Perfusion system

ABSTRACT

A perfusion container for directly administering to patients a dose of an antineoplastic drug calculated according to a patient&#39;s parameter, wherein the first perfusion container comprises a solution of antineoplastic drug at a concentration and volume such that the amount of antineoplastic drug in the container is equal to the calculated dose for one patient but less than the calculated dose for a second patient, the calculated dose is provided to first patient within 5% variance by directly administering the full volume of the solution of antineoplastic drug from the first perfusion container, further the first perfusion container is accompanied by a second top-up perfusion container comprising a solution of antineoplastic drug at a concentration and volume such that the calculated dose is provided within 5% variance by directly administering the full volume of the solution of antineoplastic drug from the first perfusion container and the second top-up container to the second patient.

FIELD OF THE INVENTION

The present invention relates to a perfusion system for directlyadministering to patients in need thereof a dose of an antineoplasticdrug calculated according to a patient parameter.

BACKGROUND OF THE INVENTION

There are certain drawbacks associated with most of the commerciallyavailable parenteral dosage forms of antineoplastic drugs. For instance,the commercially available parenteral dosage forms are available as vialproducts having either lyophilized powder of drug or concentratedsolutions which cannot be directly administered to a patient; ratherthey require manipulation.

Particularly, in case of lyophilized compositions, in addition to therequirement of reconstitution of the freeze dried powder, itsmanufacturing process is itself very complicated and expensive. Further,when the composition is in the form of a concentrated solution, there isan additional step of dilution prior to administration. Thesedifficulties only multiply, when the dose of the drug is to be deliveredin terms of the patient parameter, such as body surface area, renalclearance, in which cases the dose needs to be accurately calculated anddilution and/or reconstitutions need to be done taking care of theprecision aspect of the dose of the drug. While attempting to deliverthe accurate dose of the drug, surplus volume of reconstituted ordiluted solution may be required or withdrawal of the volume may berequired. These additional steps may provide a threat or risk ofcontamination or loss of sterility etc. or exposure of the cytotoxicdrug to the involved personnel (workers, pharmacists, medical personnel,nurses). Since the patient parameter can vary over a very wide range, itbecomes practically very difficult to cater to the precise dose of thedrug.

Thus, given many potential hazards and errors associated with the use ofthe prior known products, there is therefore a need to provide aperfusion system for enabling hospitals or clinics to directlyadminister to patients in need thereof, a dose of an antineoplastic drugcalculated according to a patient parameter, wherein the parametervaries over a range in the patient population. The present inventionfulfills this need. The present invention provides a perfusion systemcomprising plurality of perfusion containers in different sets, eachfilled with an aqueous, ready-to-infuse perfusion solution of theantineoplastic drug and which enables hospitals or clinics to administera dose of an antineoplastic drug calculated according to at least onepatient parameter, to patients in need thereof, while avoiding any ofthe steps of manipulation, dilution, reconstitution, dispensing,sterilization, transfer, handling or compounding before intravenousadministration.

SUMMARY OF THE INVENTION

The present invention provides a perfusion system for enabling hospitalsor clinics to directly administer to patients in need thereof a dose ofan antineoplastic drug calculated according to a patient parameter,wherein the parameter varies over a range in the patient population,said system comprising:

-   -   plurality of perfusion containers, each container comprising a        ready-to-infuse, aqueous perfusion solution of an antineoplastic        drug, wherein said plurality of perfusion containers comprise a        first set of perfusion container (s) comprising a        ready-to-infuse, aqueous perfusion solution of an antineoplastic        drug and a second set of top-up perfusion containers comprising        a ready-to-infuse, aqueous perfusion solution of the        antineoplastic drug and optionally a third set of top-up        perfusion containers comprising a ready-to-infuse, aqueous        perfusion solution of the antineoplastic drug, and    -   instructions for selecting one or more perfusion container(s)        from the first set and if required one or more top-up perfusion        container(s) from the second and/or third set for directly        administering the calculated dose of the antineoplastic drug        from the selected perfusion containers

The present invention further provides a method for directlyadministering to a patient in need thereof a dose of an antineoplasticdrug calculated according to a patient parameter, wherein the parametervaries over a range in the patient population, the method comprising thesteps of:

-   -   providing the perfusion system of the present invention;    -   calculating the dose according to a patient parameter, selecting        one or more perfusion container(s) from the first set of        perfusion container(s) and if necessary from the second and/or        third set of top-up perfusion container(s) required for directly        administering the calculated dose and    -   directly administering to the patient in need thereof the        perfusion solution in the selected containers.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The term “ready-to-infuse” or ‘directly administer’ or ‘directlyadministering’ or ‘direct intravenous infusion’ as used herein refers todirect intravenous infusion of the aqueous solution of antineoplasticdrug to the patient without involving any intermediate steps ofmanipulation, dilution, reconstitution, dispensing, sterilization,transfer, handling or compounding before intravenous parenteraladministration of the drug solution to the patient. The aqueous drugsolution can be directly administered parenterally from the perfusioncontainer. Suitably, the perfusion system and the method according tothe present invention avoids any manipulation, any step ofreconstituting or dilution such as those involved in conventionallyophilized or concentrated products. It further does not involve anystep of transfer of infusion solution from one container to anotherbefore administration or any volume adjustment, i.e. addition orwithdrawal of the aqueous solution from the perfusion container, beforeadministration. The term “ready-to-infuse’ or ‘directly administer’ or‘directly administering’ or ‘direct intravenous infusion’ also includeswithin its meaning administering the perfusion solution present in theperfusion container without the need to monitor the volume perfused.This eliminates the risk of any potential calculation or dilution erroras well as risk of microbiological contamination prior toadministration. This also eliminates or minimizes contact of the drugsby hospital personnel, thus avoiding any potential side effectsassociated with the cytotoxic anti-neoplastic drugs. The terms“ready-to-infuse’ or ‘directly administer’ or ‘directly administering’or ‘direct intravenous infusion’ also means that the perfusioncontainers are filled with the aqueous perfusion solution of theantineoplastic drug and subjected to sterilization process in thepharmaceutical manufacturing facility. This is different from hospitalcompounding, which involves intermediate steps of dispensing or mixingof the aqueous solution which has been manufactured separately in amanufacturing plant or site and supplied in bulk volumes to the hospitalor pharmacy. The term ‘directly administer’ excludes any transfer of thesolution from a bulk container such as used in a pharmacy into theperfusion container from where the solution is intravenouslyadministered.

Hereinafter, the terms “ready-to-infuse’ or ‘directly administer’ or‘directly administering’ or ‘direct intravenous infusion’ as used in thespecification should be understood to refer to the meaning as definedherein.

The term ‘perfusion’ as used herein in the present invention, refers tothe intravenous infusion or administration of a solution of a drug to apatient.

The term ‘calculated dose’ or ‘dose calculated according to at least onepatient parameter’ as used herein means the dose of the antineoplasticdrug that is to be administered to the patient depending upon thedisease condition or indication and the patient parameters such as bodysurface area, body weight, renal clearance or hepatic function and otherfactors, that may affect the dose calculation.

The term “administering the calculated dose” as used herein meansadministering the calculated dose with precision. For example as shownin illustrative tables (a) to (m), as the body surface area increases byincrements of 0.1 mg/m² there is or are available perfusion containersin the set, for delivery of a precise dose. The tables illustrate thatthe precise dose is within ±5% of the calculated dose.

The term ‘instructions’ as used herein refers to the instructionsaccompanying the perfusion system of the present invention, which may bein the form of a written or electronic communication. The instructionsmay be provided with one or more perfusion container(s) of the perfusionsystem or a single set of instructions with the perfusion system or maybe made available electronically. The instructions involve directionsfor arriving at the dose desired for a patient based on patientparameter and for appropriately selecting perfusion containers from thefirst or second or third set of perfusion containers and for directlyadministering the drug from the perfusion containers to deliver thedesired dose within ±5% variance. The electronic instructions may be inthe form of a chip or barcode which correspond to the instructions thatcan be read with the help of an electronic device.

The present invention provides a perfusion system for enabling hospitalsor clinics to directly administer a dose of an antineoplastic drugcalculated according to at least one patient parameter, to patients inneed thereof, wherein the parameter varies over a range in the patientpopulation. The direct administration avoids any of the steps ofmanipulation, dilution, reconstitution, dispensing, sterilization,transfer, handling or compounding before intravenous administration.

The antineoplastic drugs that may be used according to the presentinvention includes, but are not limited to cisplatin, carboplatin,oxaliplatin, vincristine, vinblastine, vinorelbine, vindesine,pemetrexed, gemcitabine, irinotecan, topotecan, methotrexate, docetaxel,paclitaxel, doxorubicin, daunonibicin, epirubicin, idarubicin,streptozocin, mitomycin, gentamicin, tenoposide, 5-fluorouracil,ifosfamide, cyclophosphamide, mechlorethamine, carmustine, dacarbazine,cladribine, clofarabine, fulvestrant, pegfilgrastim, pamidronate,zoledronic acid, mitoxantrone, leukovorin, etoposide, triplatin,picoplatin, satraplatin, lobaplatin or pharmaceutically acceptable saltsthereof. According to some preferred embodiments, the antineoplasticdrugs include platinum complex compounds such as cisplatin, carboplatinand oxaliplatin; vinca alkaloid drugs such as vincristine, vinblastine,vinorelbine, vindesine, antifolates such as pemetrexed; nucleosidemetabolic inhibitor such as gemcitabine, topoisomerase inhibitor such asirinotecan or pharmaceutically acceptable salts thereof. The amount orconcentration of the antineoplastic drugs in the perfusion system of thepresent invention is expressed in terms of the acid or base of theantineoplastic agent. The amount of antineoplastic drug is expressed interms of the base used and when a salt is used, the amount may beconverted into equivalent weight.

The perfusion system can be configured for a particular dosing regimenby using a specific concentration that can cater to a relatively widerrange of patient population, such as for example patient populationhaving body surface area varying from 1.4 to 2.6, preferable 1.6 to 2.1.For example for an anti-neoplastic drug irinotecan, such a specificconcentration was found to be 0.7 mg/ml for a dosing regimen requiring125 mg/m² or 180 mg/m² dose to be administered or a specificconcentration was found to be 1.2 mg/ml for a dosing regimen requiring350 mg/m² dose to be administered. For example for anotheranti-neoplastic drug carboplatin, such a specific concentration wasfound to be 2.0 mg/ml for a dosing regimen requiring 200 mg/m² dose tobe administered. For example for another anti-neoplastic drug docetaxel,such a specific concentration was found to be 0.3 mg/ml for a dosingregimen requiring 55 mg/m² dose to be administered. For example foranother anti-neoplastic drug oxaliplatin, such a specific concentrationwas found to be 0.7 mg/ml for a dosing regimen requiring 85 mg/m² doseto be administered. For example for another anti-neoplastic druggemcitabine, such a specific concentration was found to be 10.0 mg/mlfor a dosing regimen requiring 1000 mg/m² or 1250 mg/m² dose to beadministered. For certain antineoplastic drugs, it was found that acombination of two different such specific concentrations could also beused to cater to a relatively wider range of patient population, such asfor example patient population having body surface area varying from 1.4to 2.6, preferable 1.6 to 2.1. Such drugs include cisplatin, topotecan,irinotecan, carboplatin, oxaliplatin, vincristine, vinblastine,vinorelbine, azacitidine, pemetrexed, gemcitabine, paclitaxel,cyclophosphamide, docetaxel, arsenic trioxide, fluorouracil and thelike. For example, for an anti-neoplastic drug paclitaxel at a dose of50 mg/m², the concentration of solution was found to be 0.5 mg/ml infirst perfusion container and 0.4 mg/ml in the second set of top-upperfusion container. For example, for an anti-neoplastic drug irinotecanat a dose of 180 mg/m², the concentration of solution was found to be1.5 mg/ml in first perfusion container and 0.2 mg/ml in the second setof top-up perfusion container.

In some embodiments the perfusion system comprises a kit with perfusioncontainers of two or more antineoplastic drugs so as to cater to thedesired doses as per combination regimens. For example in case ofcolorectal cancer combination regimen, a combination of irinotecan,leucovorin and 5-fluorouracil needs to be administered and thecombination regimen involves administering 180 mg/m2 irinotecan asintravenous infusion over 90 minutes on days 1, 15 and 29 withleucovorin 200 mg/m² intravenous infusion over two hours on days 1, 2,15, 16, 29 and 30 followed by 5-fluorouracil 400 mg/m² intravenous bolusinfusion on days 1, 2, 15, 16, 29 and 30 and 5-fluorouracil 600 mg/m²intravenous infusion over 22 hours on days 1, 2, 15, 16, 29 and 30.

In some embodiments, the perfusion system according to the presentinvention comprises plurality of perfusion containers prepared in largescale manufacturing unit, each container comprising a ready-to-infuse,aqueous perfusion solution of an antineoplastic drug. The plurality ofperfusion containers according to the present invention includes a firstset of perfusion container(s) comprising a ready-to-infuse, aqueousperfusion solution of an antineoplastic drug and a second set of top-upperfusion containers comprising a ready-to-infuse, aqueous perfusionsolution of the antineoplastic drug and optionally a third set of top-upperfusion containers comprising a ready-to-infuse, aqueous perfusionsolution of the antineoplastic drug. The number of containers per setmay range from one to fifteen containers. For instance, each set ofcontainers may include 1 to 10 containers having varying amount of theantineoplastic drug per container. The perfusion system further includesinstructions to the user such as pharmacist or hospital staff to selectappropriate number of containers from one or more set of the perfusioncontainers so as to administer the calculated dose with precision.Suitably the precise dose delivered is equal to or within ±5%,preferably within ±3% of a dose calculated according to at least onepatient parameter.

Whereas in some embodiments, the number of containers in each set may beselected such that for almost the entire patient population with varyingpatient parameter such as body surface area or weight, a combination ofcontainers to deliver the calculated dose can be found. There areprovided other embodiments that target a smaller population with anarrower range of patient parameter. In such embodiments, the number ofcontainers per set is 1, 2, 3, 4, 5, 6, 7 and not more than 10. Inpreferred embodiments, the number of first perfusion containers may be 5and the number of second top-up containers may be 1, 2, 3, 4, 5, 6, 7,8, 9 or 10, preferably, 1 or 2 or 3.

In a more preferred example there is provided one container from thefirst set and a second container from the second set. For example, foran antineoplastic drug with a dose of 180 mg/m², the first set has onlyone container having a concentration of antineoplastic drug at 1.5 mg/mland a volume of 200 ml, and second set has only two containers eachhaving a concentration of antineoplastic drug at 0.2 mg/ml and a volumeof 150 ml. The set can be used for accurate dosing of patients with bodysurface area in the range 1.6 to 2.1 mg/m² as illustrated below:

First Perfusion Top-up perfusion container, 200 ml container, 150 ml(blue band) (red band) Antineoplastic drug Antineoplastic drug atconcentration at concentration of 1.5 mg/ml of 0.3 mg/ml: Total TargetVolume of Dose delivered Volume of Dose delivered % Variation** Dose tobe perfusion from perfusion top up from top up Total dose from deliveredBSA delivered container container container container delivered dose Vscalculated (m²) (mg) D (ml) (a) (mg) (ml) (b) (mg) (mg) (a + b) dose 1.6288 200 300 0 0 300 4.2 1.7 306 200 300 0 0 300 −2.0 1.8 324 200 300 10030 330 1.9 1.9 342 200 300 100 30 330 −3.5 2.0 360 200 300 100 × 2 60360 0.0 2.1 378 200 300 100 × 2 60 360 −4.8 **% Variation from delivereddose Vs calculated dose = [((a + b) − D]/D × 100

The perfusion system of above Table is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.6 and 1.7 Infuse the full volume from one 200 mlcontainer with blue band 1.8 and 1.9 Infuse the full volume from one 200ml container with blue band and full volume from one 100 ml top-upcontainer with red band 2.0 and 2.1 Infuse the full volume from one 200ml container with blue band and full volume from two 100 ml top-upcontainers with red band

Thus accordingly the present invention provides a perfusion containerfor directly administering to patients a dose of an antineoplastic drugcalculated according to a patient's parameter, wherein the firstperfusion container comprises a solution of antineoplastic drug at aconcentration and volume such that the amount of antineoplastic drug inthe container is equal to the calculated dose for one patient but lessthan the calculated dose for a second patient, the calculated dose isprovided to first patient within 5% variance by directly administeringthe full volume of the solution of antineoplastic drug from the firstperfusion container, further the first perfusion container isaccompanied by a second top-up perfusion container comprising a solutionof antineoplastic drug at a concentration and volume such that thecalculated dose is provided within 5% variance by directly administeringthe full volume of the solution of antineoplastic drug from the firstperfusion container and the second top-up container to the secondpatient.

According to one embodiment, the concentrations the concentration in thefirst perfusion container and the concentration in the second top-upperfusion container is same. According to one preferred embodiment, theconcentration in the first perfusion container is higher than theconcentration in the second top-up perfusion container.

According to one embodiment, the volume in the first perfusion containerand the volume in the second top-up perfusion container is same.According to one preferred embodiment, the volume in the perfusioncontainer is higher than the volume in the second top-up perfusioncontainer.

Alternatively, the present invention also provides a perfusion containerfor directly administering to a patient a dose of an antineoplastic drugcalculated according to the patient's parameter, wherein the perfusioncontainer comprises a solution of antineoplastic drug at a concentrationand volume such that the amount of antineoplastic drug in the containeris less than the calculated dose, further wherein the perfusioncontainer is accompanied by a second top-up perfusion containercomprising a solution of antineoplastic drug at a concentration andvolume such that the calculated dose is provided within 5% variance bydirectly administering the full volume of the solution of antineoplasticdrug from the first perfusion container and the second top-up container.

According to one embodiment, the concentrations and volumes of perfusionsolution in the selected set of containers are such that for each dosecalculated according to a parameter for any given patient in the patientpopulation, a first container and if necessary top-up perfusioncontainer(s) can be selected to deliver the dose by administering thefull volume in the selected containers without the need to monitor thevolume of perfusion solution administered and the dose is delivered withprecision. The dose can be delivered with precision, i.e. within ±5%variance, preferably within ±3% variance from the calculated dose.

According to one embodiment of the present invention, there is provideda perfusion container configured to be one of perfusion containers, inthe perfusion system of the present invention, wherein the perfusioncontainer comprises a ready to infuse perfusion solution of a partialdose of an antineoplastic drug for some patients in the patientpopulation, wherein the dose is calculated according to a patientparameter.

According to the present there is further provided a method for directlyadministering to a patient in need thereof a dose of an antineoplasticdrug calculated according to a patient parameter, wherein the parametervaries over a range in the patient population, the method comprising thesteps of: providing the perfusion system of the present invention;calculating the dose according to a patient parameter, selecting one ormore perfusion container(s) from the first set of perfusion container(s)and if necessary from the second and/or third set of top-up perfusioncontainer(s) required for directly administering the calculated dose anddirectly administering to the patient in need thereof the perfusionsolution in the selected containers.

The perfusion system and method of the present invention advantageouslythus covers a range of patient population having wide range of patientparameter. For instance, when the patient parameter is body surface area(BSA), it is generally known to vary over a range of 1.2 to 2.8 mg/m² ina patient population. The perfusion system and method of the presentinvention advantageously covers the whole range of such a patientpopulation and is suitable to directly administer the calculated dosewith precision, which is achieved because of the unique configuration ofthe perfusion system of the present invention.

According to the present invention, there is provided instructions forarriving at the dose of antineoplastic drug desired for a patient inneed thereof, based on one of patient parameter and for appropriatelyselecting one or more perfusion container(s) from the first set and ifrequired one or more top-up perfusion container(s) from the secondand/or third set perfusion containers and for directly administering theantineoplastic drug from the selected perfusion containers to deliverthe desired calculated dose with precision. The instructions may be inthe form of written instructions or electronic instruction or any othersuitable form accompanying the perfusion system and/or with one or moreperfusion container of the perfusion system. The written instructionsmay be in the form of a package insert or labeling. The electronicinstructions may be in the form of a chip or barcode which correspond tothe instructions that can be read with the help of an electronic device.Preferably the instructions are written instructions accompanying theperfusion system and/or with one or more perfusion container of theperfusion system.

The perfusion system and method according to the present inventioncomprises a first set of perfusion containers comprising aready-to-infuse, aqueous perfusion solution of an antineoplastic drug ata first concentration, a second set of top-up perfusion containerscomprising a ready-to-infuse, aqueous perfusion solution of theantineoplastic drug at a second concentration and optionally a third setof top-up perfusion containers comprising a ready-to-infuse, aqueousperfusion solution of the antineoplastic drug at a third concentration.

According to one embodiment of the present invention, the first, secondand/or third concentrations may be same or different. Preferably,according to one embodiment, the first, second and/or thirdconcentrations are different. According to one embodiment, the first,second and/or third concentrations are same.

According to one embodiment of the present invention, the volume ofsolution in the individual containers may be same or different.Preferably, according to one embodiment, the volume of solution in theindividual containers is different. According to one embodiment, thevolume of solution in the individual containers is same.

According to one preferred embodiment of the present invention, thefirst concentration, the second concentration and/or third concentrationare different. According to this embodiment, the volume of solution inthe first set, second set and/or third set of containers may be same ordifferent. In one preferred embodiment, the first, second and/or thirdconcentrations are different and the volume of solution in the first setis different from the volume of solution in the second set and/or thirdset of containers. In another embodiment, the first, second and/or thirdconcentrations are different and the volume of solution in the first setand in the second set and/or third set of containers is same.

According to one embodiment of the present invention, the first, secondand/or third concentrations are same. According to this embodiment, thevolume of solution in the first set, second set and/or third set ofcontainers are different.

According to one embodiment of the present invention, the first set ofperfusion containers and the second set of top-up perfusion containers,and/or the third set of top-up perfusion containers each comprise aplurality of containers containing different volumes of ready-to-infuse,aqueous perfusion solution of an antineoplastic drug.

According to another preferred embodiment, the first, second and/orthird concentrations are different and the first concentration is higherthan the second and/or third concentration, further wherein the volumeof solution in the first set is higher than the volume of solution inthe second set and/or third set of containers. According to anotherembodiment, the first, second and/or third concentrations are different,further wherein the first concentration is higher than the second and/orthird concentration, further wherein the volume of solution in the firstset is lower than the volume of solution in the second set and/or thirdset of containers.

In one preferred embodiment, the perfusion system comprises the firstset, the second set as well as the third set of perfusion containers. Inone embodiment, the first concentration is higher than the secondconcentration and the second concentration is higher than the thirdconcentration. In another embodiment, the first concentration is higherthan the second concentration and the second concentration is same asthe third concentration.

In one embodiment for antineoplastic drugs such as vincristine,vinblastine, vinorelbine, oxaliplatin, cisplatin, and the like whosedose based on the body surface area (mg/m²) is low, the concentration ofdrug in the solution of the first set may be lower than theconcentration of drug in the solution of second set and/or third set,and the volume of solution in the first set is higher than the volume ofsolution in the second set and/or third set of containers.

In another embodiment, for antineoplastic drugs such as gemcitabine,pemetrexed, carboplatin or irinotecan whose dose based on the bodysurface area (mg/m²) is high, the concentration of drug in the solutionof the first set is preferably higher than the concentration of drug inthe solution of second set and/or third set, and the volume of solutionin the first set may be higher or lower, preferably higher, than thevolume of solution in the second set and/or third set of containers.

According to the present invention, the set of containers of theperfusion system may range in volume from a lower to a higher volume.The volume of the aqueous solution of drug contained in differentperfusion containers may vary from about 10 ml to about 5000 ml,preferably from about 20 ml to about 2000 ml, more preferably from about25 ml to about 1000 ml. In preferred embodiments, the different set ofperfusion containers having different volumes may be distinguished. Inparticular, the different sets of perfusion containers may be visuallydistinguished, for example through the use of different patterns orcolors on some or all of the containers. In particular different colorsmay be used for labeling.

According to the present invention, the aqueous perfusion solution maycomprise parenterally acceptable, pharmaceutically acceptable excipientsor adjuvants. The excipients that may be used are selected from but notlimited to pH adjusting and/or buffering agents, tonicity adjustingagents, chelating agents, solvents etc.

In preferred embodiments, the perfusion container according to thepresent invention may be a perfusion bag, infusion bag, flexible pouch,infusion bottle. The container is made up of a suitable material such asplastic or other polymeric material or glass. The container may besingle or multiple layered. In one embodiment, the perfusion containershave a single outlet for withdrawal of the aqueous solution from thecontainer while being administered intravenously. This design avoids anymanipulation, such as volume adjustment (addition or removal of aqueoussolution) prior to intravenous infusion.

The perfusion container according to the present invention does notinclude devices such as syringes or autoinjectors, pen or any containerthat has a needle attached to it, through which the solution would bedelivered, and that has low volume capacity such as 1-20 ml. Suchcontainers are known to be used in the prior art to adjust thecalculated dose of the drug in the main infusion container bytransferring the drug solution from another container to the infusioncontainer or withdrawing a volume of drug solution from the infusioncontainer before administering to the patient.

The perfusion system of the present invention allows the hospital staffto select perfusion containers like infusion bags according to thecalculated dose from a set and directly without any manipulation infusethe full volume from each infusion bag to the patient. This does notinvolve any manipulation or handling in hospital pharmacy and avoids anyadjustment of contents and therefore any errors in dose or exposure ofthe formulation or exposure of the staff to the cytotoxic formulation.

In one embodiment, the perfusion containers may be packaged in asecondary packaging that surrounds the perfusion container. Thesecondary packaging may comprise a second container such as a pouch oroverwrap or carton. The secondary packaging may comprise a suitablepouch, such as an aluminum pouch covering the perfusion container. Theoverwrap pouch may have a layer of oxygen absorbing material. Thesecondary packaging may further comprise an oxygen scavenger that may beplaced in between the perfusion container and overwrap/pouch. In onepreferred embodiment, the secondary packaging comprises both an aluminumpouch and an oxygen scavenger.

The perfusion system comprising containers filled with aqueous solutionof anti-neoplastic drug according to the present invention are useful inthe treatment of cancer or neoplastic disorders. In one preferredembodiment, wherein the drug is Irinotecan hydrochloride, the perfusionsystem is useful for the treatment of metastatic colorectal cancerwherein the target dose of irinotecan to be delivered is based on bodysurface area (BSA). It may be used as a Colorectal Combination Regimens,wherein 125 mg/m² intravenous (i.v.) infusion is administered over 90minutes on Days 1, 8, 15, 22 in 6-week cycles with 5-flourouracil andleucovorin. It may alternatively be used at 180 mg/m² as an i.v.infusion over 90 minutes on Days 1, 15, 29 in 6-week cycles with5-flourouracil and leucovorin. It may also be used as a ColorectalSingle-Agent Regimens wherein 125 mg/m² i.v. infusion is administeredover 90 minutes on Days 1, 8, 15, 22 followed by a 2-week rest or it mayalternatively be used as 350 mg/m² i.v. infusion over 90 minutes onceevery 3 weeks.

Suitably, the perfusion system of the present invention is sterile. Theterm “sterile” as used in the context of the invention, means that theaqueous solution has been brought to a state of sterility and thesolution complies with the sterility requirements of the standardPharmacopoeias like United States Pharmacopoeias (USP). Sterilizationmay be achieved by suitable techniques such as filtration sterilization,radiation sterilization and the like.

Illustrations

According to one embodiment, there is provided a perfusion system foradministration of irinotecan or its pharmaceutical acceptable salts andor hydrates thereof. Table 1 below provide details of the perfusionsystem having containers of first and second set with the ranges ofconcentration and volume of the solution or irinotecan per set.

TABLE 1 Perfusion system of Irinotecan: First set of Second set of topup Perfusion container perfusion container Concentration range (mg/ml)1.0-3.0 0.1-0.8 Preferred concentration range 1.5-2.0 0.2-0.4 (mg/ml)Volume range (ml)  80-500  50-350 Preferred volume range (ml)  90-300 75-150

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second set. Insome embodiments, the first set of perfusion containers contain solutionhaving higher irinotecan concentration then the solution in second setof top-up perfusion containers. In some embodiments, the first set ofperfusion container and second set of top-up perfusion containerscontain solution having same irinotecan concentration, but differentvolume. Preferably the volume of solution in the first set of perfusioncontainers is higher than that in the second set of top-up containers.

In one preferred embodiment, the first set of infusion containerscomprise perfusion solution having irinotecan or its pharmaceuticalacceptable salts at a concentration ranging from about 1.0 mg/ml to 3.0mg/ml and volume of solution ranging from about 80 ml to about 500 ml,further wherein the second or third set of infusion containers compriseperfusion solution having irinotecan at a concentration ranging fromabout 0.1 to 0.8 mg/ml and volume of solution ranging from about 50 mlto about 350 ml. The amount of irinotecan mentioned herein in theexamples refers to the concentration of irinotecan base. When thesolution contain a pharmaceutical acceptable salt or hydrate ofirinotecan, the amount in mg/ml of the salt or hydrate will be higherdepending upon the type of salt or hydrate and the said salt or hydratewill have an equivalent amount of irinotecan depending upon themolecular weight. For instance, if irinotecan hydrochloride trihydrateis used in amounts of 1.5 mg/ml, the equivalent amount of irinotecanthat it will contain will be 1.3 mg/ml.

In one embodiment, irinotecan is used for the treatment of colorectalcancer and it may be either administered as a combination regimen havingirinotecan, leucovorin and 5-fluorouracil or as a single agent regimen.Combination regimen 1 involves administering 125 mg/m² irinotecan asintravenous infusion over 90 minutes on days 1, 8, 15 and 22 withleucovorin 20 mg/m² intravenous bolus infusion on days 1, 8, 15, 22followed by 5-fluorouracil 500 mg/m² intravenous bolus infusion on days1, 8, 15, and 22 every 6-weeks. Combination regimen 2 involvesadministering 180 mg/m² irinotecan as intravenous infusion over 90minutes on days 1, 15 and 29 with leucovorin 200 mg/m² intravenousinfusion over two hours on days 1, 2, 15, 16, 29 and 30 followed by5-fluorouracil 400 mg/m² intravenous bolus infusion on days 1, 2, 15,16, 29 and 30 and 5-fluorouracil 600 mg/m² intravenous infusion over 22hours on days 1, 2, 15, 16, 29 and 30. Single-Agent Regimen 1 involves125 mg/m² i.v. infusion, administered over 90 minutes on Days 1, 8, 15,22 followed by a 2-week rest. Single-Agent Regimen 2 involves 350 mg/m²i.v. infusion over 90 minutes once every 3 weeks.

The perfusion system of the present invention is so configured that itprovides the desired target dose of irinotecan (within ±5% of variation)as per the regimens illustrated above and can cater to a relativelywider range of patient population, such as for example patientpopulation having body surface area varying from 1.4 to 2.6, preferable1.6 to 2.1 using limited number of perfusion containers.

As illustrated below in Table 2, for combination regimen 1 andsingle-agent regimen 1, (having irinotecan dose of 125 mg/m²), it ispossible to have the following kit with 5 containers and with followinginstructions to cater to the desired target dose of irinotecan forpatient population having body surface area varying from 1.3 to 2.6:

TABLE 2 Description of perfusion system of Irinotecan according to oneembodiment: Top-up perfusion First set of Perfusion containers-container Drug Second set Drug concentration - 0.7 mg/ml:concentration - 0.7 mg/ml: Total Target Volume delivered Dose deliveredVolume delivered Dose at from first from first from second Dosedelivered % Variation** 125 mg/m2 to perfusion perfusion top up fromtop-up Total dose from delivered BSA be delivered container containerperfusion container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) container (ml) (b) (mg) (mg) (a + b) dose 1.3 162.5 240 168 0 0 1683.4 1.4 175 240 168 0 0 168 −4.0 1.5 187.5 270 189 0 0 189 0.8 1.6 200240 168 50 35 203 1.5 1.7 212.5 240 168 50 35 203 −4.5 1.8 225 270 18950 35 224 −0.4 1.9 237.5 240 168 100 70 238 0.2 2.0 250 270 189 100 70259 3.6 2.1 262.5 270 189 100 70 259 −1.3 2.2 275 400 280 0 0 280 1.82.3 287.5 400 280 0 0 280 −2.6 2.4 300.0 400 280 50 35 315 5.0 2.6 325.0400 280 50 35 315 −3.1 **% Variation from delivered dose Vs calculateddose = [((a + b) − D]/D × 100

The abbreviation BSA as used in the illustrations stands for patient'sBody Surface Area.

The containers of the perfusion system of Table (2) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containersIrinotecan containers; Irinotecan concentration 0.7 mg/ml concentration0.7 mg/ml: Volume of perfusion Alphabetical Volume of top upAlphabetical container (ml) Code container (ml) Code 240 A 50 D 270 B100 E 400 C

The perfusion system of above Table (2) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 and 1.4 Infuse the full volume from one 240 mlcontainer having an alphabetical code A 1.5 Infuse the full volume fromone 270 ml container having an alphabetical code B 1.6 and 1.7 Connectone 240 ml container having an alphabetical code A to one 50 mlcontainer having an alphabetical code D and infuse the full volume 1.8Connect one 270 ml container having an alphabetical code B to one 50 mlcontainer having an alphabetical code D and infuse the full volume 1.9Connect one 240 ml container having an alphabetical code A to one 100 mlcontainer having an alphabetical code E and Infuse the full volume 2.0and 2.1 Connect one 270 ml container having an alphabetical code B toone 100 ml container having an alphabetical code E and Infuse the fullvolume 2.2 and 2.3 Infuse the full volume from one 400 ml containerhaving an alphabetical code C 2.4 and 2.6 Connect one 400 ml containerhaving an alphabetical code C to one 50 ml container having analphabetical code D and infuse the full volume

As illustrated below in Table 3, for combination regimen 2, (havingirinotecan dose of 180 mg/m²), it is possible to have the following kitwith 5 containers and with following instructions to cater to thedesired target dose of irinotecan for patient population having bodysurface area varying from 1.3 to 2.6:

TABLE 3 Description of perfusion system of Irinotecan according to oneembodiment: First set of Perfusion Second set of top-up perfusioncontainers Irinotecan containers; Irinotecan concentration 0.7 mg/mlconcentration 0.7 mg/ml: Total Target Volume of Dose delivered Volume ofDose delivered % Variation** Dose to be perfusion from perfusion top upfrom top-up Total dose from delivered BSA* delivered container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (mg) (a + b) dose 1.3 234 350 245 0 0 245 3.8 1.4 252350 245 0 0 245 −2.8 1.5 270 350 245 50 35 280 3.7 1.6 288 350 245 50 35280 −2.8 1.7 306 450 315 0 0 315 2.9 1.8 324 450 315 0 0 315 −2.8 1.9342 450 315 50 35 350 2.3 2 360 450 315 50 35 350 −2.8 2.1 378 550 385 00 385 1.9] 2.2 396 550 385 0 0 385 −2.8 2.3 414 550 385 50 35 420 1.42.4 432 550 385 50 35 420 −2.8 2.5 450 550 455 100 70 455 1.1 2.6 468550 455 100 70 455 −2.8 **% Variation from delivered dose Vs calculateddose = [((a + b) − D]/D × 100

The containers of the perfusion system of Table (3) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containersIrinotecan containers; Irinotecan concentration 0.7 mg/ml concentration0.7 mg/ml: Volume of perfusion Alphabetical Volume of top upAlphabetical container (ml) code container (ml) code 350 F 50 D 450 G100 E 550 H

The perfusion system of above Table (3) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 and 1.4 Infuse the full volume from one 350 mlcontainer having an alphabetical code F 1.5 and 1.6 Connect one 350 mlcontainer having an alphabetical code F to one 50 ml container having analphabetical code D and infuse the full volume 1.7 and 1.8 Infuse thefull volume from one 450 ml container having an alphabetical code G 1.9and 2.0 Connect one 450 ml container having an alphabetical code G toone 50 ml container having an alphabetical code D and infuse the fullvolume 2.1 and 2.2 Connect one 550 ml container having an alphabeticalcode H and Infuse the full volume 2.3 and 2.4 Connect one 550 mlcontainer having an alphabetical code H to one 50 ml container having analphabetical code D and Infuse the full volume 2.5 and 2.6 Connect one550 ml container having an alphabetical code H to one 100 ml containerhaving an alphabetical code E and Infuse the full volume

As illustrated below in Table 4, for combination regimen 4, (havingirinotecan dose of 350 mg/m²), it is possible to have the following kitwith 5 containers and with following instructions to cater to thedesired target dose of irinotecan for patient population having bodysurface area varying from 1.3 to 2.4:

TABLE 4 Description of perfusion system of Irinotecan according to oneembodiment: Top-up perfusion First set of Perfusion containers -container Drug Second set Drug concentration - 1.2 mg/ml:concentration - 1.2 mg/ml: Volume delivered Dose delivered Volumedelivered Total Target from first from first from second Dose delivered% Variation** Dose to be perfusion perfusion top up from top-up Totaldose from delivered BSA delivered container container perfusioncontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg)container (ml) (b) (mg) (a + b) dose 1.3 455 mg 370 444 0 0 444 −2.4 1.4490 mg 370 444 50 60 504 2.9 1.5 525 mg 450 540 0 0 540 2.8 1.6 560 mg450 540 0 0 540 −3.6 1.7 595 mg 450 540 50 60 600 0.8 1.8 630 mg 450 54050 60 600 −4.8 1.9 665 mg 570 684 0 0 684 2.9 2.0 700 mg 570 684 0 0 684−2.9 2.1 735 mg 570 684 50 60 744 1.5 2.2 770 mg 650 780 0 0 780 1.3 2.3805 mg 650 780 0 0 780 −3.1 2.4 840 mg 650 780 50 60 840 0

The containers of the perfusion system of Table (4) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containersIrinotecan containers; Irinotecan concentration 1.2 mg/ml concentration1.2 mg/ml: Volume of perfusion Alphabetical Volume of top upAlphabetical container (ml) code container (ml) code 370 I 50 M 450 J570 K 650 L

The perfusion system of above Table (4) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 Infuse the full volume from one 370 mlcontainer having an alphabetical code I 1.4 Connect one 370 ml containerhaving an alphabetical code I to one 50 ml container having analphabetical code M and infuse the full volume 1.5 and 1.6 Infuse thefull volume from one 450 ml container having an alphabetical code J1.7and 1.8 Connect one 450 ml container having an alphabetical code J toone 50 ml container having an alphabetical code M and infuse the fullvolume 1.9 and 2.0 Infuse the full volume from one 570 ml containerhaving an alphabetical code K 2.1 Connect one 570 ml container having analphabetical code K to one 50 ml container having an alphabetical code Mand infuse the full volume 2.2 and 2.3 Infuse the full volume from one650 ml container having an alphabetical code L 2.4 Connect one 650 mlcontainer having an alphabetical code L to one 50 ml container having analphabetical code M and infuse the full volume

For meeting all the dosage requirements (covering all approved dosageregimens for irinotecan and covering wide range of patient population,such as for example patient population having body surface area varyingfrom 1.4 to 2.6), 13 containers coded A to M are required but for eachpatient only one or 2 containers are used at any one time. In case whentwo perfusion containers are to be infused to a patient then they may beconnected with a Y connector. The perfusion containers have a singleoutlet for withdrawal of the aqueous solution from the container whilebeing administered intravenously. This design avoids any manipulation,such as volume adjustment (addition or removal of aqueous solution)prior to intravenous infusion.

In another embodiment, there are provided perfusion containers in thefirst set having drug solution at higher concentration and top-upperfusion containers having drug solution at lower concentration. Thedose of Irinotecan for a particular indication is 180 mg/m² based onpatient's body surface area. There is provided instructions to calculatethe total dose to be delivered to a patient based on the body surfacearea and select one container from the first set and one container fromthe top-up perfusion container to deliver the calculated dose within ±5%variance. This is presented in table 5 below:

TABLE (5) Description of perfusion system of Irinotecan according to oneembodiment: First set of Perfusion Second set of top-up perfusioncontainers Irinotecan containers; Irinotecan concentration 1.5 mg/mlconcentration 0.2 mg/ml: Total Target Volume of Dose delivered Volume ofDose delivered % Variation** Dose to be perfusion from perfusion top upfrom top-up Total dose from delivered BSA* delivered container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (mg) (a + b) dose 1.3 234 160 240 0 0 240 2.6 1.4 252160 240 0 0 240 −4.8 1.5 270 160 240 150 30 270 0.0 1.6 288 200 300 0 0300 4.2 1.7 306 200 300 0 0 300 −2.0 1.8 324 200 300 150 30 330 1.9 1.9342 200 300 150 30 330 −3.5 2 360 240 360 0 0 360 0.0 2.1 378 240 360150 30 390 3.2 2.2 396 240 360 150 30 390 −1.5 2.3 414 280 420 0 0 4201.4 2.4 432 280 420 0 0 420 −2.8 2.5 450 280 420 150 30 450 0.0 2.6 468280 420 150 30 450 −3.8 **% Variation from delivered dose Vs calculateddose = [((a + b) − D]/D × 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (5) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containersIrinotecan containers; Irinotecan concentration 1.5 mg/ml concentration0.2 mg/ml: Volume of perfusion Alphabetical Volume of top upAlphabetical container (ml) code container (ml) code 160 O 150 S 200 P240 Q 280 R

The perfusion system of Table (5) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 and 1.4 Infuse the full volume from one 160 mlcontainer having an alphabetical code O 1.5 Connect one 160 ml containerhaving an alphabetical code O to one 150 ml container having analphabetical code S and Infuse the full volume 1.6 and 1.7 Connect one200 ml container having an alphabetical code P and one 150 ml containerhaving an alphabetical code S and and Infuse the full volume 1.8 and 1.9Connect one 200 ml container having an alphabetical code P to one 150 mlcontainer having an alphabetical code S and Infuse the full volume 2.0Infuse the full volume from one 240 ml container having an alphabeticalcode Q 2.1 and 2.2 Connect one 240 ml container having an alphabeticalcode Q to one 150 ml container having an alphabetical code S and Infusethe full volume 2.3 and 2.4 Infuse the full volume from one 280 mlcontainer having an alphabetical code R 2.5 and 2.6 Connect one 280 mlcontainer having an alphabetical code R and one 150 ml container havingan alphabetical code S and Infuse the full volume

As described above, the target dose of Irinotecan for a person having aspecific body surface area can be delivered (within ±5% variance), bythe perfusion system of the present invention, by infusing the fullvolume of solution from the selected perfusion containers of the firstset and top-up perfusion containers from the second set.

In another embodiment, wherein the dose of Irinotecan for a particularindication is 180 mg/m² based on patient's body surface area, there isprovided following instructions (Table 6) to calculate the total dose tobe delivered to a patient based on the body surface area and to selectone or more perfusion containers from different sets, to deliver thecalculated dose within ±5% variance.

TABLE (6) Description of perfusion system of Irinotecan according to oneembodiment: First Set of Perfusion Second Set of Top-up perfusioncontainer (200 ml) (code P) containers (150 ml) (Code S) Irinotecan atIrinotecan at concentration of 1.5 mg/ml concentration of 0.2 mg/ml:Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Patient Dose to be perfusion from perfusion top up fromtop-up Total dose from delivered BSA* delivered container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (mg) (a + b) dose 1.6 288 200 300 0 0 300 4.2 1.7 306200 300 0 0 300 −2.0 1.8 324 200 300 150 30 330 1.9 1.9 342 200 300 15030 330 −3.5 2.0 360 200 300 150 × 2 60 360 0.0 2.1 378 200 300 150 × 260 360 −4.8 **% Variation from delivered dose Vs calculated dose =[((a + b) − D]/D × 100

The perfusion system of above Table (6) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.6 and 1.7 Infuse the full volume from one 200 mlcontainer having an alphabetical code P 1.8 and 1.9 Infuse the fullvolume from one 200 ml container having an alphabetical code P and fullvolume from one 150 ml top-up container having an alphabetical code S2.0 and 2.1 Infuse the full volume from one 200 ml container having analphabetical code P and full volume from two 150 ml top-up containershaving an alphabetical code S

In the above illustration, wherever solution of two bags have to bedelivered for the desired dose, the two bags can be connected togethervia a suitable connector such as a Y connector/joint and the full volumeof solution from the two bags can be then infused. In one embodiment,the outlet of the Y joint can be connected to an infusion pump tocontrol the rate of infusion. In this embodiment, only two or three bagsare sufficient for delivering the desired calculated dose of irinotecan(within ±5% variance) for a wide range of patient population.

According to one embodiment, there is provided a perfusion system foradministration of carboplatin. The Table 7 below provide details of theperfusion system having containers of first, second and/or third setwith the ranges of concentration and volume of the solution per set.

TABLE 7 Perfusion system of Carboplatin: Second set Third set From setof First set of top up of top up container of the of Perfusion perfusionperfusion perfusion system container container container Concentrationrange 0.4-5.0 0.01-3.0 0.01-3.0 (mg/ml) Preferred concentration 1.0-3.00.01-2.0 0.01-2.0 range (mg/ml) Volume range (ml)  50-1000  30-200 30-200 Preferred volume range  50-500  30-100  30-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 8-10.

TABLE 8 Perfusion containers of the first set having carboplatin: Volumeof solution in bag Perfusion containers of first set (ml) 180 200 250300 350 400 Carboplatin amount per bag 360 400 500 600 700 800 (mg) (ata concentration of 2 mg/ml)

TABLE 9 Perfusion containers of the second set having carboplatin:Perfusion containers of second set Volume of solution in bag (ml) 50 4060 Carboplatin amount per bag 30 24 36 (mg) (at a concentration of 0.6mg/ml)

TABLE 10 Perfusion containers of the third set having carboplatin:Perfusion containers of third set Volume of solution in bag (ml) 50 4060 Carboplatin amount per bag 20 16 24 (mg) (at a concentration of 0.4mg/ml)

In preferred embodiments, the first set of infusion containers compriseperfusion solution having carboplatin at a concentration ranging fromabout 0.4 mg/ml to 5.0 mg/ml and volume of solution ranging from about50 ml to about 1000 ml, further wherein the second or third set ofinfusion containers comprise perfusion solution having carboplatin at asecond and/or third concentration ranging from about 0.01 mg/ml to 2.5mg/ml and volume of solution ranging from about 30 ml to about 100 ml;further wherein the perfusion solution has a pH ranging from about 3.0to 7.0.

In one specific embodiment, the dose of carboplatin for a particularindication is 360 mg/m² based on patient's body surface area. There isprovided instructions to calculate the total dose to be delivered to apatient based on the body surface area and select one container from thefirst set and one or more container from the top-up perfusion containerto deliver the calculated dose within ±5% variance and is presented intable (11) below:

TABLE 11 Description of perfusion system of carboplatin according to oneembodiment: First set of Perfusion Second set of Top-up perfusioncontainer having containers having carboplatin at 2.0 mg/ml carboplatinat 0.8 mg/ml Total Target Volume of Dose delivered Volume of Dosedelivered % Variation Dose to be perfusion from perfusion top up fromtop-up Total dose from delivered BSA delivered container containercontainer container delivered dose Vs calculated (m²) D (mg) (ml) (a)(mg) (ml) (b) (mg) (mg) (a + b) dose 1.5 540.0 270 540 0 0 0 0 1.6 576.0270 540 65 52 592 2.7 1.7 612.0 270 540 65 52 592 −3.3 1.8 648.0 330 6600 0 660 1.9 1.9 684.0 330 660 0 0 660 −3.5 2.0 720.0 330 660 65 52 712−1.1 **% Variation from delivered dose Vs calculated dose = [((a + b) −D]/D × 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (11) may be color codedas follows:

First set of Perfusion Second set of top-up perfusion containerscarboplatin containers; carboplatin concentration 2.0 mg/mlconcentration 0.8 mg/ml: Volume of perfusion Alphabetical Volume of topup Alphabetical container (ml) code container (ml) code 270 A 65 C 330 B

The perfusion system of above Table (11) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.5 Infuse the full volume from one 270 mlcontainer having an alphabetical code A 1.6 and 1.7 Connect one 270 mlcontainer having an alphabetical code A to one 65 ml top-up containerhaving an alphabetical code C and infuse the full volume 1.8 and 1.9Infuse the full volume from one 330 ml container having an alphabeticalcode B 2.0 Connect one 330 ml container having an alphabetical code B toone 65 ml top-up container having an alphabetical code C and Infuse thefull volume

In one specific embodiment, the dose of carboplatin for a particularindication is 300 mg/m² based on patient's body surface area. There isprovided instructions to calculate the total dose to be delivered to apatient based on the body surface area and select one or more perfusioncontainers of carboplatin from different sets, to deliver the calculateddose within ±5% variance and is presented in table (12) below:

TABLE (12) Description of perfusion system of carboplatin according toone embodiment: Second Set of Top-up Third Set of Top-up First set ofPerfusion perfusion containers; perfusion containers- container;Carboplatin Carboplatin Carboplatin concentration - 2.0 mg/mlconcentration - 0.6 mg/ml: concentration - 0.4 mg/ml: Total TargetVolume of Dose delivered Volume of Dose delivered Volume of Dosedelivered % Variation** Dose to be perfusion from perfusion top up fromtop-up top up from top-up Total dose from delivered BSA* deliveredcontainer container container container container container delivereddose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml) (b) (mg) (ml) (c) (mg)(mg) (a + b + c) dose 1.3 390 180 360 50 30 0 0 390 0.00 1.4 420 180 36050 30 50 20 410 −2.38 1.5 450 200 400 50 30 50 20 450 0.00 1.6 480 250500 0 0 0 0 500 4.2 1.7 510 250 500 0 0 0 0 500 −2.0 1.8 540 250 500 5030 50 20 550 1.9 1.9 570 250 500 50 × 2 60 0 0 560 −1.8 2.0 600 300 6000 0 0 0 600 0.00 2.1 630 300 600 50 30 0 0 630 0.00 2.2 660 300 600 5030 50 20 650 −1.5 2.3 690 350 700 0 0 0 0 0 1.4 2.4 720 350 700 0 0 5020 720 0.00 **% Variation from delivered dose Vs calculated dose =[((a + b + c) − D]/D × 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (12) may be color codedas follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers perfusion containers; perfusion containers; Carboplatinconcen- Carboplatin concen- Carboplatin concen- tration 2.0 mg/mltration 0.8 mg/ml: tration 0.4 mg/ml: Volume of Volume of Volume ofperfusion Alpha- top up Alpha- top up Alpha- container betical containerbetical container betical (ml) code (ml) code (ml) code 180 D 50 I 50 J200 E 250 F 300 G 350 H

The perfusion system of Table (12) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 Connect one 180 ml container having analphabetical code D to one 50 ml container having an alphabetical code Iand infuse the full volume 1.4 Connect one 180 ml container having analphabetical code D + one 50 ml container having an alphabetical codeI + one 50 ml container having an alphabetical code J and infuse thefull volume 1.5 Connect one 200 ml container having an alphabetical codeE + one 50 ml container having an alphabetical code I band and one 50 mlcontainer having an alphabetical code J and infuse the full volume 1.6and 1.7 Infuse the full volume from one 250 ml container having analphabetical code F 1.8 Connect one 250 ml container having analphabetical code F + one 50 ml container having an alphabetical codeI + one 50 ml container having an alphabetical code J and infuse thefull volume 1.9 Connect one 250 ml container having an alphabetical codeF to two 50 ml container having an alphabetical code I and infuse thefull volume 2.0 Infuse the full volume from one 300 ml container havingan alphabetical code G 2.1 Connect one 300 ml container having analphabetical code G and one 50 ml container having an alphabetical codeI and infuse the full volume 2.2 Connect one 300 ml container having analphabetical code G + one 50 ml container having an alphabetical codeI + one 50 ml container having an alphabetical code J and infuse thefull volume 2.3 Infuse the full volume from one 350 ml container havingan alphabetical code H 2.4 Connect one 350 ml container having analphabetical code H to one 50 ml container having an alphabetical code Jand infuse the full volume

In another specific embodiment, the dose of carboplatin for a particularindication is 360 mg/m² based on patient's body surface area. There isprovided instructions to calculate the total dose to be delivered to apatient based on the body surface area and select one or more perfusioncontainers of carboplatin from different sets, to deliver the calculateddose within ±5% variance and is presented in table (13) below:

TABLE (13) Description of perfusion system of carboplatin according toone embodiment: Second set of Top-up Third set of Top-up First set ofPerfusion perfusion containers- perfusion containers- containerCarboplatin Carboplatin Carboplatin concentration - 2.2 mg/ml:concentration - 0.6 mg/ml: concentration - 0.4 mg/ml: Total TargetVolume of Dose delivered Volume of Dose delivered Volume of Dosedelivered % Variation** Dose to be perfusion from perfusion top up fromtop-up top up from top-up Total dose from delivered BSA* deliveredcontainer container container container container container delivereddose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml) (b) (mg) (ml) (c) (mg)(a + b + c) dose 1.2 432 180.0 396 0 0 50 20 416 −3.7 1.3 468 180 396100 60 0 0 456 −2.6 1.4 504 200 440 100 60 0 0 500 −0.8 1.5 540 250 5500 0 0 0 550 1.9 1.6 576 250 550 0 0 50 20 570 −1.0 1.7 612 250 550 10060 0 0 610 −0.3 1.8 648 300 660 0 0 0 0 660 1.9 1.9 684 300 660 0 0 5020 680 −0.6 2.0 720 300 660 100 60 0 0 720 0 2.1 756 350 770 0 0 0 0 7701.9 2.2 792 350 770 0 0 50 20 790 −0.3 2.3 828 350 770 100 60 0 0 8300.2 2.4 864 350 770 100 60 50 20 850 −1.6 2.6 936 400 880 100 60 0 0 9400.4 **% Variation from delivered dose Vs calculated dose = [((a + b + c)− D]/D × 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (13) may be color codedas follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers perfusion containers; perfusion containers; Carboplatinconcen- Carboplatin concen- Carboplatin concen- tration 2.2 mg/mltration 0.6 mg/ml: tration 0.4 mg/ml: Volume of Volume of Volume ofperfusion top up Alpha- top up Alpha- container Alphabetical containerbetical container betical (ml) code (ml) code (ml) code 180 K 100 Q 50 R200 L 250 M 300 N 350 O 400 P

The perfusion system of Table (13) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Connect one 180 ml container having analphabetical code K to one 50 ml container having an alphabetical code Rand infuse the full volume 1.3 Connect one 180 ml container having analphabetical code K to one 100 ml container having an alphabetical codeQ and infuse the full volume 1.4 Connect one 200 ml container having analphabetical code L to one 100 ml container having an alphabetical codeQ and infuse the full volume 1.5 Infuse the full volume from one 250 mlcontainer having an alphabetical code M 1.6 Connect one 250 ml containerhaving an alphabetical code M to one 50 ml container having analphabetical code R and infuse the full volume 1.7 Connect one 250 mlcontainer having an alphabetical code M to one 100 ml container havingan alphabetical code Q and infuse the full volume 1.8 Infuse the fullvolume from one 300 ml container having an alphabetical code N 1.9Connect one 300 ml container having an alphabetical code N to one 50 mlcontainer having an alphabetical code R and infuse the full volume 2.0Connect one 300 ml container having an alphabetical code N to one 100 mlcontainer having an alphabetical code Q and infuse the full volume 2.1Infuse the full volume from one 350 ml container having an alphabeticalcode O 2.2 Connect one 350 ml container having an alphabetical code O toone 50 ml container having an alphabetical code R and infuse the fullvolume 2.3 Connect one 350 ml container having an alphabetical code O toone 100 ml container having an alphabetical code Q and infuse the fullvolume 2.4 Connect one 350 ml container having an alphabetical code O +one 100 ml container having an alphabetical code Q + one 50 ml containerhaving an alphabetical code R and infuse the full volume 2.6 Connect one400 ml container with having an alphabetical code P to one 100 mlcontainer having an alphabetical code Q and infuse the full volume

In one specific embodiment, the dose of carboplatin for a particularindication is 200 mg/m² based on patient's body surface area. There isprovided instructions to calculate the total dose to be delivered to apatient based on the body surface area and select one or more perfusioncontainers from different sets, to deliver the calculated dose within±5% variance and is presented in table (14) below:

TABLE (14) Description of perfusion system of carboplatin according toone embodiment: Second set of Top-up perfusion First set of Perfusioncontainers; Carboplatin container; Carboplatin concentration 2.0 mg/ml:concentration - 2.0 mg/ml: Volume of Dose delivered Total Target Volumeof Dose delivered top up from top-up % Variation Dose to be perfusionfrom perfusion perfusion perfusion Total dose from delivered BSA *delivered container container container container delivered dose Vscalculated (m²) D (mg) (ml) (a) (mg) (ml) (b) (mg) (mg) (a + b) dose 1.6320.0 160 320.0 0 0 320.0 0.0 1.7 340.0 125 250.0 50 100 350.0 2.9 1.8360.0 125 250.0 50 100 350.0 −2.8 1.9 380.0 190 380.0 0 0 380.0 0.0 2.0400.0 125 250.0 80 160 410.0 2.5 2.1 420.0 125 250.0 80 160 410.0 −2.42.2 440.0 145 290.0 80 160 450.0 2.3 2.3 460.0 145 290.0 80 160 450.0−2.2 2.4 480.0 245 490.0 0 0 490.0 2.1 **% Variation from delivered doseVs calculated dose = [((a + b + c) − D]/D × 100 * BSA—Body Surface Area

The containers of the perfusion system of Table (14) may be color codedas follows:

First set of Perfusion Second set of top-up perfusion containersCarboplatin containers; Carboplatin concentration 2.0 mg/mlconcentration 2.0 mg/ml: Volume of perfusion Color Volume of top upColor container (ml) code container (ml) code 125 S 50 X 160 T 80 Y 190U 145 V 245 W

The perfusion system of Table (14) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.6 Infuse the full volume from one 160 mlcontainer having an alphabetical code T 1.7 and 1.8 Connect one 125 mlcontainer having an alphabetical code S to one 50 ml container having analphabetical code X and infuse the full volume 1.9 Infuse the fullvolume from one 190 ml container having an alphabetical code U 2.0 and2.1 Connect one 125 ml container having an alphabetical code S and one80 ml container having an alphabetical code Y and infuse the full volume2.2 and 2.3 Connect one 145 ml container having an alphabetical code Vto one 80 ml container having an alphabetical code Y and infuse the fullvolume 2.4 Infuse the full volume from one 245 ml container having analphabetical code W

As described above, the target dose of carboplatin for a person having aspecific body surface area can be delivered (within ±5% variance), bythe perfusion system of the present invention, by infusing the fullvolume of solution from the selected perfusion containers of the firstset and top-up perfusion containers from the second and/or third set.

According to one embodiment, there is provided a perfusion system foradministration of topotecan or its pharmaceutically acceptable salt.Table 15 below provides details of the perfusion system havingcontainers of first, second and/or third set with the ranges ofconcentration and volume of the solution per set.

TABLE 15 Perfusion system of topotecan: Second set Third set From set ofFirst set of top up of top up container of of perfusion perfusionperfusion the perfusion system container container containerConcentration range 0.001 to 0.072 0.0005-0.003  0.003-0.005  (mg/ml)Preferred concentration 0.01 0.002 0.004 range (mg/ml) Volume range (ml)50-500 30-200 30-200 Preferred volume range 50-340 50-100 50-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 16-18.

TABLE 16 Perfusion containers of the first set having topotecan:Perfusion containers of first set Volume of solution in bag (ml) 50 100160 250 340 400 450 500 Topotecan amount per bag 0.5 1.0 1.6 2.5 3.4 4.04.5 5.0 (mg) (at a concentration of 0.01 mg/ml)

TABLE 17 Perfusion containers of the second set having topotecan:Perfusion containers of second set Volume of solution in bag (ml) 50 75100 200 Topotecan amount per bag (mg) 0.1 0.15 0.2 0.4 (at aconcentration of 0.002 mg/ml)

TABLE 18 Perfusion containers of the third set having topotecan:Perfusion containers of third set Volume of solution in bag (ml) 50 75100 Topotecan amount per bag (mg) 0.2 0.3 0.4 (at a concentration of0.004 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis topotecan, the first set of infusion containers comprise perfusionsolution having topotecan at a concentration ranging from about 0.001mg/ml to 0.072 mg/ml and volume of solution ranging from about 50 ml toabout 500 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having topotecan at aconcentration ranging from about 0.0005-0.005 mg/ml and volume ofsolution ranging from about 30 ml to about 100 ml.

In one specific embodiment, the dose of topotecan for a particularindication is 1.5 mg/m² based on patient's body surface area. There isprovided instructions for calculating the total dose to be delivered toa patient based on the body surface area and instructions for selectingone container from the first set and one container from the top-upperfusion container to deliver the calculated dose within ±5% varianceand is presented in table (19) below.

TABLE 19 Description of perfusion system of Topotecan according to oneembodiment: First set of Perfusion Second set of Top-up perfusioncontainers; (250 ml, containers (50 ml, code B; code A) topotecan 200 mlcode C); topotecan concentration 0.01 mg/ml concentration 0.002 mg/ml:Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA* delivered container container containercontainer delivered dose Vs calculated (m²) D (mg) (ml) (a) (mg) (ml)(b) (mg) (mg) (a + b) dose 1.6 2.4 250 2.5 0 0 2.5 −4.3 1.7 2.55 250 2.550 0.1 2.6 −2.0 1.8 2.7 250 2.5 50 0.1 2.6 −3.7 1.9 2.85 250 2.5 200 0.42.9 1.8 2.0 3 250 2.5 200 0.4 2.9 −3.3 **% Variation from delivered doseVs calculated dose = [((a + b) − D]/D × 100 *BSA—Body Surface Area

The perfusion system of above Table (19) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.6 Infuse the full volume from one 250 mlcontainer having an alphabetical code A 1.7 and 1.8 Infuse the fullvolume from one 250 ml container having an alphabetical code A and fullvolume from one 50 ml top- up container having an alphabetical code B1.9 and 2.0 Infuse the full volume from one 250 ml container having analphabetical code A and full volume from one 200 ml top- up containershaving an alphabetical code C

In one specific embodiment, the dose of topotecan for a particularindication is 1.5 mg/m² based on patient's body surface area. There isprovided instructions for calculating the total dose to be delivered toa patient based on the body surface area and instructions for selectingone or more perfusion containers of topotecan from first set and one ormore top-up perfusion container from the second and/or third set oftop-up perfusion containers, to deliver the calculated dose within ±5%variance and is presented below in table (20):

TABLE (20) Description of perfusion system of topotecan according to oneembodiment: First set of Perfusion Second set of Top-up Third set ofTop-up container topotecan perfusion containers; perfusion containers;concentration topotecan concentration topotecan concentration 0.01 mg/ml0.002 mg/ml: 0.004 mg/ml: Total Target Volume of Dose delivered Volumeof Dose delivered Volume of Dose delivered % Variation** Dose to beperfusion from perfusion top up from top-up top up from top-up Totaldose from delivered BSA* delivered container container containercontainer container container delivered dose Vs calculated (m²) (mg) D(ml) (a) (mg) (ml) (b) (mg) (ml) (c) (mg) (mg) (a + b + c) dose 1.4 2.1160 1.6 0 0 100 0.4 2.0 −4.8 1.5 2.25 160 1.6 100 0.2 100 0.4 2.2 −2.21.6 2.4 250 2.5 0 0 0 0 2.5 4.2 1.7 2.55 250 2.5 0 0 0 0 2.5 −2.0 1.82.7 250 2.5 100 0.2 0 0 2.7 0.0 1.9 2.85 250 2.5 0 0 100 0.4 2.9 1.8 2 3250 2.5 0 0 100 0.4 2.9 −3.3 2.1 3.15 250 2.5 100 0.2 100 0.4 3.1 −1.62.2 3.3 340 3.4 0 0 0 0 3.4 3.0 2.3 3.45 340 3.4 0 0 0 0 3.4 −1.4 2.43.6 340 3.4 100 0.2 0 0 3.6 0.0 **% Variation from delivered dose Vscalculated dose = [((a + b + c) − D]/D × 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (20) may be color codedas follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers perfusion containers; perfusion containers; topotecan concen-topotecan concen- topotecan concen- tration 0.01 mg/ml tration 0.002mg/ml: tration 0.004 mg/ml: Volume of Volume of Volume of perfusionAlpha- top up Alpha- top up Alpha- container betical container beticalcontainer betical (ml) code (ml) code (ml) code 160 D 250 A 100 F 100 G340 E

The perfusion system of Table (20) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.4 Connect one 160 ml container having analphabetical code D to one 100 ml container having an alphabetical codeF and infuse the full volume 1.5 Infuse the full volume from one 160 mlcontainer having an alphabetical code D+; one 100 ml container having analphabetical code F + one 100 ml container having an alphabetical code G1.6 and 1.7 Infuse the full volume from one 250 ml container having analphabetical code A 1.8 Connect one 250 ml container having analphabetical code A and one 100 ml container having an alphabetical codeF and infuse the full volume 1.9 and 2.0 Connect one 250 ml containerhaving an alphabetical code A and one 100 ml container having analphabetical code G and infuse the full volume 2.1 Connect one 250 mlcontainer having an alphabetical code A + one 100 ml container having analphabetical code G + one 100 ml container having an alphabetical code Fand infuse the full volume 2.2 and 2.3 Infuse the full volume from one340 ml container having an alphabetical code E 2.4 Connect one 340 mlcontainer having an alphabetical code E and one 100 ml container havingan alphabetical code F and infuse the full volume

As described above, the target dose of topotecan for a person having aspecific body surface area can be delivered (within ±5% variance), bythe perfusion system of the present invention, by infusing the fullvolume of solution from the selected perfusion containers of the firstset and top-up perfusion containers from the second and/or third set.

According to the present invention, the below embodiment providesperfusion system for administration of docetaxel or its pharmaceuticallyacceptable salt. Table 21 below provides details of the perfusion systemhaving containers of first, second and/or third set with the ranges ofconcentration and volume of the solution per set.

TABLE 21 Perfusion system of docetaxel Second set Third set From set ofFirst set of top up of top up container of of perfusion perfusionperfusion the perfusion system container container containerConcentration range 0.1 to 2   0.1 to 2   0.1 to 2   (mg/ml) Preferredconcentration 0.3 to 0.74 0.3 to 0.74 0.3 to 0.74 range (mg/ml) Volumerange (ml) 50-800 25-150 25-100 Preferred volume range 50-500 50-10050-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 22-24.

TABLE 22 Perfusion containers of the first set having docetaxel:Perfusion containers of first set Volume of solution in bag (ml) 185 200215 230 290 315 395 430 465 Docetaxel amount per bag 92.5 100 107.5 115135 157.5 197.5 215 232.5 (mg) (at a concentration of 0.5 mg/ml)

TABLE 23 Perfusion containers of the second set having docetaxel:Perfusion containers of second set Volume of solution in bag (ml) 50 75100 150 Docetaxel amount per bag (mg) 15 22.5 30 45 (at a concentrationof 0.3 mg/ml)

TABLE 24 Perfusion containers of the third set having docetaxel:Perfusion containers of third set Volume of solution in bag (ml) 50 75100 150 Docetaxel amount per bag (mg) 7.5 11.25 15.0 22.5 (at aconcentration of 0.15 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis docetaxel, the first set of infusion containers comprise perfusionsolution having docetaxel at a concentration ranging from about 0.1mg/ml to 2.0 mg/ml and volume of solution ranging from about 50 ml toabout 800 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having Docetaxel at aconcentration ranging from about 0.1-2.0 mg/ml and volume of solutionranging from about 25 ml to about 150 ml.

In one specific embodiment, the dose of docetaxel for a particularindication is 100 mg/m² based on patient's body surface area. There isprovided instructions to calculate the total dose to be delivered to apatient based on the body surface area and select one or more perfusioncontainers from different sets to deliver the calculated dose within ±5%variance and is presented in table (25) below.

TABLE 25 Description of perfusion system of Docetaxel according to oneembodiment: Second set of Top-up Third set of Top-up First set ofPerfusion perfusion containers; perfusion containers; container;Docetaxel Docetaxel concentration Docetaxel concentration concentration0.6 mg/ml 0.3 mg/ml: 0.15 mg/ml: Total Target Volume of Dose deliveredVolume of Dose delivered Volume Dose delivered % Variation** Dose to beperfusion from perfusion top up from top-up of top up from top-up Totaldose from delivered BSA * delivered container container containercontainer container container delivered dose Vs calculated (m²) (mg) D(ml) (a) (mg) (ml) (b) (mg) (ml) (c) (mg) (mg) (a + b + c) dose 1.6160.0 270 162 0 0 0 0 162.00 1.3 1.7 170.0 270 162 0 0 50 7.5 169.50−0.3 1.8 180.0 290 174 50 15 0 0 189.00 5.0 1.9 190.0 290 174 50 15 0 0189.00 −0.5 2 200.0 340 204 0 0 0 0 204.00 2.0 2.1 210.0 340 204 50 15 00 219.00 4.3 2.2 220.0 340 204 50 15 0 0 219.00 −0.5 2.3 230.0 340 20450 15 50 7.5 226.50 −1.5 2.4 240.0 395 237 0 0 0 0 237.0) −1.3 **%Variation from delivered dose Vs calculated dose = [((a + b + c) − D]/D× 100

The containers of the perfusion system of Table (25) may bealphabetically coded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; docetaxelconcen- docetaxel concen- docetaxel concen- tration 0.6 mg/ml tration0.3 mg/ml: tration 0.15 mg/ml: Volume of Volume of Volume of perfusionAlpha- top up Alpha- top up Alpha- container betical container beticalcontainer betical (ml) code (ml) code (ml) code 270 A 290 B 50 340 C E50 F 395 D

The perfusion system of Table (25) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.6 Infuse the full volume from one 270 mlcontainer having an alphabetical code A 1.7 Connect one 270 ml containerhaving an alphabetical code A to one 50 ml container having analphabetical code E and infuse the full volume 1.8 and 1.9 Connect one290 ml container having an alphabetical code B to one 50 ml containerhaving an alphabetical code E and infuse the full volume 2.0 Infuse thefull volume from one 340 ml container having an alphabetical code C 2.1and 2.2 Connect one 340 ml container having an alphabetical code C andone 50 ml container having an alphabetical code E and infuse the fullvolume 2.3 Connect one 340 ml container having an alphabetical code C +one 50 ml container having an alphabetical code E + one 50 ml containerhaving an alphabetical code F and infuse the full volume 2.4 Infuse thefull volume from one 395 ml container having an alphabetical code D

In one specific embodiment, the dose of docetaxel for a particularindication is 55 mg/m² based on patient's body surface area. There isprovided instructions to calculate the total dose to be delivered to apatient based on the body surface area and select one container from thefirst set and one or more container from the top-up perfusion containerto deliver the calculated dose within ±5% variance and is presented intable (26) below.

TABLE 26 Description of perfusion system of Docetaxel according to oneembodiment: Second set of Top-up First set of Perfusion perfusioncontainers; container: Docetaxel Docetaxel concentration concentration0.3 mg/ml 0.3 mg/ml: Total Target Volume of Dose delivered Volume ofDose delivered % Variation** Dose to be perfusion from perfusion top upfrom top-up Total dose from delivered BSA* delivered container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (mg) (a + b) dose 1.3 71.5 200 60 50 15 75.00 4.9 1.477.0 200 60 50 15 75.00 −2.6 1.5 82.5 270 81.00 0 0 81.00 −1.8 1.6 88.0290 87.00 0 0 87.00 −1.1 1.7 93.5 315 94.50 0 0 94.50 1.1 1.8 99.0 29087.00 50 15 102.00 3.0 1.9 104.5 290 87.00 50 15 102.00 −2.4 2 110.0 365109.50 0 0 109.50 −0.5 2.1 115.5 395 118.50 0 0 118.50 2.6 2.2 121.0 395118.50 0 0 118.50 −2.1 **% Variation from delivered dose Vs calculateddose = [((a + b) − D]/D × 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (26) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containers;docetaxel containers; docetaxel concentration 0.3 mg/ml concentration0.3 mg/ml: Volume of perfusion Alphabetical Volume of top upAlphabetical container (ml) code container (ml) code 200 G 270 A 290 B315 H 50 E 365 I 395 J

The perfusion system of Table (26) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 and 1.4 Connect one 200 ml container having analphabetical code G to one 50 ml container having an alphabetical codepink band and infuse the full volume 1.5 Infuse the full volume from one270 ml container having an alphabetical code A 1.6 Infuse the fullvolume from one 290 ml container having an alphabetical code B 1.7Infuse the full volume from one 315 ml container having an alphabeticalcode H 1.8 and 1.9 Connect one 290 ml container having an alphabeticalcode B and one 50 ml container having an alphabetical code and infusethe full volume 2.0 Infuse the full volume from one 365 ml containerhaving an alphabetical code I 2.1 and 2.2 Infuse the full volume fromone 395 ml container having an alphabetical code J

As described above, the target dose of docetaxel for a person having aspecific body surface area can be delivered (within ±5% variance), bythe perfusion system of the present invention, by infusing the fullvolume of solution from the selected perfusion containers of the firstset and top-up perfusion containers from the second and/or third set.

According to the present invention, the below embodiment providesperfusion system for administration of cisplatin. Table 27 belowprovides details of the perfusion system having containers of first,second and/or third set with the ranges of concentration and volume ofthe solution per set.

TABLE 27 Perfusion system of Cisplatin: Second set Third set From set ofFirst set of top up of top up container of of perfusion perfusionperfusion the perfusion system container container containerConcentration range 0.03-0.8  0.005-0.5  0.005-0.5  (mg/ml) Preferredconcentration 0.1-0.8 0.005 0.08 0.005-0.08 range (mg/ml) Volume range(ml) 50-1000 10-500 10-500 Preferred volume range 50-900  20-100 20-100(ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 28-30.

TABLE 28 Perfusion containers of the first set having cisplatin:Perfusion containers of first set Volume of solution in bag (ml) 500 600700 800 900 Cisplatin amount per bag (mg) 65 78 91 104 117 (at aconcentration of 0.13 mg/ml)

TABLE 29 Perfusion containers of the second set having cisplatin:Perfusion containers of second set Volume of solution in bag (ml) 50 60100 Cisplatin amount per bag 2.5 3.0 5.0 (mg) (at a concentration of0.05 mg/ml)

TABLE 30 Perfusion containers of the third set having cisplatin:Perfusion containers of third set Volume of solution in bag (ml) 40 5060 Cisplatin amount per bag 1.2 1.5 1.8 (mg) (at a concentration of 0.03mg/ml)

In one particular embodiment of the present invention wherein theantineoplastic drug is cisplatin, the first set of infusion containerscomprise perfusion solution having cisplatin at a concentration rangingfrom about 0.03 mg/ml to 0.8 mg/ml and volume of solution ranging fromabout 50 ml to about 1000 ml, further wherein the second or third set ofinfusion containers comprise perfusion solution having cisplatin at aconcentration ranging from about 0.005 mg/ml to 0.08 mg/ml and volume ofsolution ranging from about 20 ml to about 100 ml; further wherein theperfusion solution has a pH ranging from about 3.0 to 7.0.

According to one embodiment, the dose for a particular indication is 50mg/m² based on body surface area as the patient parameter. There isprovided instructions to calculate the dose based on the body surfacearea and select one or more perfusion containers of cisplatin fromdifferent sets, to deliver the calculated dose within ±5% variance andis presented in table (31) below:

TABLE (31) Description of perfusion system of cisplatin: Third set ofTop-up First set of Perfusion Second set of Top-up perfusion container;container; Cisplatin perfusion containers; Cisplatin concentrationconcentration Cisplatin concentration 0.03 mg/ml: 0.13 mg/ml: 0.05mg/ml: Volume of Total Target Volume of Dose delivered Volume of Dosedelivered top up Dose delivered % Variation** Dose to be perfusion fromperfusion top up from top-up perfusion from top-up Total dose fromdelivered BSA delivered container container container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (ml) (c) (mg) (mg) (a + b + c) dose 1.3 65 500 65 0 00 0 65 0 1.4 70 500 65 100 5 0 0 70 0 1.5 75 600 78 0 0 0 0 78 3.8 1.680 600 78 0 0 0 0 78 −2.5 1.7 85 600 78 100 5 0 0 83 −2.4 1.8 90 700 910 0 0 0 91 1.1 1.9 95 700 91 100 5 0 0 96 1.0 2.0 100 700 91 100 5 501.5 97.5 −2.6 2.1 105 800 104 0 0 0 0 104 −0.9 2.2 110 800 104 100 5 0 0109 −0.9 2.3 115 900 117 0 0 0 0 117 1.7 2.4 120 900 117 0 0 50 1.5118.5 −1.3 2.6 130 500 × 2 130 0 0 0 0 130 0.0 **% Variation fromdelivered dose Vs calculated dose = [((a + b + c) − D]/D × 100

The containers of the perfusion system of Table (31) may be alphabeticalcoded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; cisplatinconcen- cisplatin concen- cisplatin concen- tration 0.13 mg/ml tration0.05 mg/ml: tration 0.03 mg/ml: Volume of Volume of Volume of perfusionAlpha- top up Alpha- top up Alpha- container betical container beticalcontainer betical (ml) code (ml) code (ml) code 500 A 100 F 50 G 600 B700 C 800 D 900 E

The perfusion system of Table (31) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 Infuse the full volume from one 500 mlcontainer having an alphabetical code A 1.4 Connect one 500 ml containerhaving an alphabetical code A to one 100 ml container having analphabetical code F and infuse the full volume 1.5 and 1.6 Infuse thefull volume from one 600 ml container having an alphabetical code B 1.7Connect one 600 ml container having an alphabetical code B toone 100 mlcontainer having an alphabetical code F and infuse the full volume 1.8Infuse the full volume from one 700 ml container having an alphabeticalcode C 1.9 Connect one 700 ml container having an alphabetical code C toone 100 ml container having an alphabetical code F and infuse the fullvolume 2.0 Connect one 700 ml container having an alphabetical code C +one 100 ml container having an alphabetical code F + one 50 ml containerhaving an alphabetical code G and infuse the full volume 2.1 Infuse thefull volume from one 800 ml container having an alphabetical code D 2.2Connect one 800 ml container having an alphabetical code D to one 100 mlcontainer having an alphabetical code F and infuse the full volume 2.3Infuse the full volume from one 900 ml container having an alphabeticalcode E 2.4 Connect one 900 ml container having an alphabetical code E toone 50 ml container having an alphabetical code G and infuse the fullvolume 2.6 Infuse the full volume from two 500 ml container having analphabetical code A

According to another embodiment, the table (32) below gives instructionsfor calculation of the dose and instructions for selecting one or moreperfusion containers of cisplatin from different sets, at a dose of 100mg/m², in accordance with body surface area as the patient parameter, todeliver the calculated dose within ±5% variance:

TABLE (32) Description of perfusion system of cisplatin: First set ofPerfusion Second set of Top-up container; Cisplatin perfusioncontainers; concentration - Cisplatin concentration - 0.26 mg/ml: 0.10mg/ml: Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA delivered container container containercontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml)(b) (mg) (mg) (a + b) dose 1.3 130 500 130 0 0 130 0.0 1.4 140 500 130100 10 140 0.0 1.5 150 600 156 0 0 156 4.0 1.6 160 600 156 50 5 161 0.61.7 170 600 156 100 10 166 −2.4 1.8 180 700 182 0 0 182 1.1 1.9 190 700182 100 10 192 1.1 2 200 700 182 100 10 192 −4.0 2.1 210 800 208 0 0 208−0.9 2.2 220 800 208 100 10 218 −0.9 2.3 230 900 234 0 0 234 1.7 2.4 240900 234 50 5 239 −0.4 2.6 260 1000.0 260 0 0 260 0.00 **% Variation fromdelivered dose Vs calculated dose = [((a + b) − D]/D × 100

The containers of the perfusion system of Table (32) may be alphabeticalcoded as follows:

First set of Perfusion Second set of top-up perfusion containers;cisplatin containers; cisplatin concentration 0.13 mg/ml concentration0.05 mg/ml: Volume of perfusion Alphabetical Volume of top upAlphabetical container (ml) code container (ml) code 500 H 50 N 600 I100 O 700 J 800 K 900 L 1000 M

The perfusion system of Table (32) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.3 Infuse the full volume from one 500 mlcontainer having an alphabetical code H 1.4 Connect one 500 ml containerhaving an alphabetical code H to one 100 ml container having analphabetical code O and infuse the full volume 1.5 Infuse the fullvolume from one 600 ml container having an alphabetical code I 1.6Connect one 600 ml container having an alphabetical code I to one 50 mlcontainer having an alphabetical code N and infuse the full volume 1.7Connect one 600 ml container having an alphabetical code I to one 100 mlcontainer having an alphabetical code O and infuse the full volume 1.8Infuse the full volume from one 700 ml container having an alphabeticalcode J 1.9 and 2.0 Connect one 700 ml container having an alphabeticalcode J to one 100 ml container having an alphabetical code O and infusethe full volume 2.1 Infuse the full volume from one 800 ml containerhaving an alphabetical code K 2.2 Connect one 800 ml container having analphabetical code K to one 100 ml container having an alphabetical codeO and infuse the full volume 2.3 Infuse the full volume from one 900 mlcontainer having an alphabetical code L 2.4 Connect one 900 ml containerhaving an alphabetical code L to one 50 ml container having analphabetical code N and infuse the full volume 2.6 Infuse the fullvolume from one 1000 ml container having an alphabetical code M

As described above, the target dose of docetaxel for a person having aspecific body surface area can be delivered (within ±5% variance), bythe perfusion system of the present invention, by infusing the fullvolume of solution from the selected perfusion containers of the firstset and top-up perfusion containers from the second and/or third set.

According to the present invention, the below embodiment providesperfusion system for administration of oxaliplatin. Table 33 belowprovides details of the perfusion system having containers of first,second and/or third set with the ranges of concentration and volume ofthe solution per set.

TABLE 33 Perfusion system of Oxaliplatin: Second set Third set From setof First set of top up of top up container of the of perfusion perfusionperfusion perfusion system container container container Concentrationrange 0.4-2.0 0.05-1.25 0.05-1.25 (mg/ml) Preferred concentration0.6-1.0 0.1-0.5 0.1-0.5 range (mg/ml) Volume range (ml)  50-1000  25-500 25-500 Preferred volume range  70-500  25-100  25-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Table 34-36:

TABLE 34 Perfusion containers of the first set having oxaliplatin:Perfusion containers of first set Volume of solution in bag (ml) 150 180220 260 300 Oxaliplatin amount per bag 105 126 154 182 210 (mg) (at aconcentration of 0.7 mg/ml)

TABLE 35 Perfusion containers of the second set having oxaliplatinPerfusion containers of second set Volume of solution in bag (ml) 50 4060 Oxaliplatin amount per bag 7.5 6.0 9.0 (mg) (at a concentration of0.15 mg/ml)

TABLE 36 Perfusion containers of the third set having oxaliplatinPerfusion containers of third set Volume of solution in bag (ml) 50 4060 Oxaliplatin amount per bag 5.0 4.0 6.0 (mg) (at a concentration of0.10 mg/ml)

In one particular embodiment of the present invention wherein theantineoplastic drug is oxaliplatin, the first set of infusion containerscomprise perfusion solution having oxaliplatin at a concentrationranging from about 0.4 mg/ml to 2.0 mg/ml and volume of solution rangingfrom about 50 ml to about 1000 ml, further wherein the second or thirdset of infusion containers comprise perfusion solution havingoxaliplatin at a concentration ranging from about 0.05 mg/ml to 0.25mg/ml and volume of solution ranging from about 20 ml to about 100 ml;further wherein the perfusion solution has a pH ranging from about 3.0to 7.0.

According to one embodiment, the antineoplastic drug is oxaliplatin andthe dose for a particular indication is 85 mg/m² based on body surfacearea as the patient parameter. There is provided instructions tocalculate the dose based on the body surface area of the patient andselect appropriately one or more perfusion containers of oxaliplatinfrom different sets, to deliver the calculated dose within ±5% varianceand is presented in table (37) below:

TABLE (37) Description of perfusion system of oxaliplatin: First set ofPerfusion Second set of Top-up perfusion container Oxaliplatincontainers; Oxaliplatin concentration - concentration - 0.7 mg/ml: 0.15mg/ml: Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA* delivered container container containercontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml)(b) (mg) (a + b) dose 1.2 102 150 105 0 0 105 2.9 1.4 119 150 105 100 15120 0.8 1.5 127.5 180 126 0 0 126 −1.2 1.6 136 180 126 50 7.5 133.5 −1.81.7 144.5 180 126 100 15 141 −2.4 1.8 153 220 154 0 0 154 0.7 1.9 161.5220 154 50 7.5 161.5 0.0 2.0 170 220 154 100 15 169 −0.6 2.1 178.5 260182 0 0 182 1.96 2.2 187 260 182 50 7.5 189.5 1.3 2.3 195.5 260 182 10015 197 0.8 2.4 204 260 182 100 15 19 −3.4 2.6 221 300 210 100 15 225 1.8**% Variation from delivered dose Vs calculated dose = [((a + b) − D]/D× 100 *BSA—Body Surface Area

The containers of the perfusion system of Table (37) may be alphabeticalcoded as follows:

First set of Perfusion Second set of top-up perfusion containers;oxaliplatin containers; oxaliplatin concentration 0.7 mg/mlconcentration 0.15 mg/ml: Volume of perfusion Alphabetical Volume of topup Alphabetical container (ml) code container (ml) code 150 A 50 F 180 B100 G 220 C 260 D 300 E

The perfusion system of Table (37) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Infuse the full volume from one 150 mlcontainer having an alphabetical code A 1.4 Connect one 150 ml containerhaving an alphabetical code A to one 100 ml container having analphabetical code G and infuse the full volume 1.5 Infuse the fullvolume from one 180 ml container having an alphabetical code B 1.6Connect one 180 ml container having an alphabetical code B to one 50 mlcontainer having an alphabetical code F and infuse the full volume 1.7Connect one 180 ml container having an alphabetical code B to one 100 mlcontainer having an alphabetical code G and infuse the full volume 1.8Infuse the full volume from one 220 ml container having an alphabeticalcode C 1.  Connect one 220 ml container having an alphabetical code C toone 50 ml container having an alphabetical code F and infuse the fullvolume 2.0 Connect one 220 ml container having an alphabetical code C toone 100 ml container having an alphabetical code G and infuse the fullvolume 2.1 Infuse the full volume from one 260 ml container having analphabetical code D 2.2 Connect one 260 ml container having analphabetical code D to one 50 ml container having an alphabetical code Fand infuse the full volume 2.3 and 2.4 Connect one 260 ml containerhaving an alphabetical code D to one 100 ml container having analphabetical code G and infuse the full volume 2.6 Connect one 300 mlcontainer having an alphabetical code E to one 100 ml container havingan alphabetical code G and infuse the full volume

According to another embodiment, the table (38) below gives instructionsfor calculating the dose and instructions for selecting one or moreperfusion containers of oxaliplatin from different sets, at a dose of 85mg/m², in accordance with body surface area as the patient parameter, todeliver the calculated dose within ±5% variance:

TABLE (38) Description of perfusion system of oxaliplatin: Third set ofTop-up First set of Perfusion Second set of Top-up perfusion containers;container oxaliplatin perfusion containers; oxaliplatin concentrationconcentration - oxaliplatin concentration 0.7 mg/ml: 0.7 mg/ml: 0.7mg/ml: Volume of Total Target Volume of Dose delivered Volume of Dosedelivered top up Dose delivered % Variation** Dose to be perfusion fromperfusion top up from top-up perfusion from top-up Total dose fromdelivered BSA delivered container container container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (ml) (c) (mg) (a + b + c) dose 1.2 102 100 70 50 35 00 105 2.9 1.3 110.5 100 70 50 35 0 0 105 −4.97 1.4 119 120 84 50 35 0 0119 0.0 1.5 127.5 130 91 50 35 0 0 126 −1.2 1.6 136 145 102 50 35 0 0137 0.4 1.7 144.5 160 112 50 35 0 0 147 1.7 1.8 153 160 112 50 35 0 0147 −3.9 1.9 161.5 170 119 50 35 0 0 154 −4.6 2 170 145 102 0 0 100 70172 1.2 2.1 178.5 160 112 0 0 100 70 182 2.0 2.2 187 160 112 0 0 100 70182 −2.7 2.3 195.5 180 126 0 0 100 70 196 0.3 2.4 204 180 126 0 0 100 70196 −3.9 2.5 212.5 160 112 50 35 100 70 217 2.1 2.6 221 180 126 50 35100 70 231 4.5 **% Variation from delivered dose Vs calculated dose =[((a + b + c) − D]/D × 100

The containers of the perfusion system of Table (38) may be alphabeticalcoded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; oxaliplatinconcen- oxaliplatin concen- oxaliplatin concen- tration 0.7 mg/mltration 0.7 mg/ml: tration 0.7 mg/ml: Volume of Volume of Volume ofperfusion Alpha- top up Alpha- top up Alpha- container betical containerbetical container betical (ml) code (ml) code (ml) code 100 H 50 N 100 O120 I 130 J 145 K 160 L 170 M 180 B

The perfusion system of Table (38) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 and 1.3 Connect one 100 ml container having analphabetical code H and one 50 ml container having an alphabetical codeN and infuse the full volume 1.4 Connect one 120 ml container having analphabetical code I and one 50 ml container having an alphabetical codepink and infuse the full volume 1.5 Connect one 130 ml container havingan alphabetical code J and one 50 ml container having an alphabeticalcode J and infuse the full volume 1.6 Connect one 145 ml containerhaving an alphabetical code K and one 50 ml container havinganalphabetical code N and infuse the full volume 1.7 and 1.8 Connect one160 ml container having an alphabetical code L and one 50 ml containerhaving an alphabetical code N and infuse the full volume 1.9 Connect one170 ml container having an alphabetical code M and one 50 ml containerhaving an alphabetical code N and infuse the full volume 2.0 Connect one145 ml container having an alphabetical code K and one 100 ml containerhaving an alphabetical code O and infuse the full volume 2.1 and 2.2Connect one 160 ml container having an alphabetical code L and one 100ml container having analphabetical code O and infuse the full volume 2.3and 2.4 Connect one 180 ml container having an alphabetical code B andone 100 ml container having analphabetical code O and infuse the fullvolume 2.5 Connect one 160 ml container having an alphabetical code L +one 50 ml container having analphabetical code N + one 100 ml containerhaving an alphabetical code O and infuse the full volume 2.6 Connect one180 ml container having an alphabetical code B + one 50 ml containerhaving analphabetical code N + one 100 ml container having analphabetical code O and infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers todeliver the calculated target dose within ±5% of variation.

According to the present invention, the below embodiment providesperfusion system for administration of vinorelbine or itspharmaceutically acceptable salt such as vinorelbine tartrate. Table 39below provides details of the perfusion system having containers offirst, second and/or third set with the ranges of concentration andvolume of the solution per set.

TABLE 39 Perfusion system of Vinorelbine: Second set Third set From setof First set of top up of top up container of the of perfusion perfusionperfusion perfusion system container container container Concentrationrange 0.2-2.5 0.01-1.25  0.01-1.25  (mg/ml) Preferred concentration0.5-1.5 0.01-0.8  0.01-0.8  range (mg/ml) Volume range (ml)  25-100020-500 20-500 Preferred volume range  60-600 20-100 20-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 40-42.

TABLE 40 Perfusion containers of the first set having vinorelbine:Perfusion containers of first set Volume of solution in bag (ml) 70 80100 120 140 160 Vinorelbine amount per bag 35 40 50 60 70 80 (mg) (at aconcentration of 0.5 mg/ml)

TABLE 41 Perfusion containers of the second set having vinorelbine:Perfusion containers of second set Volume of solution in bag (ml) 40 5060 Vinorelbine amount per bag 2 2.5 3 (mg) (at a concentration of 0.05mg/ml)

TABLE 42 Perfusion containers of the third set having vinorelbine:Perfusion containers of third set Volume of solution in bag (ml) 40 50Vinorelbine amount per bag 1 1.25 (mg) (at a concentration of 0.025mg/ml)

In one particular embodiment of the present invention wherein theantineoplastic drug is vinorelbine, the first set of infusion containerscomprise perfusion solution having vinorelbine at a concentrationranging from about 0.2 mg/ml to 2.5 mg/ml and volume of solution rangingfrom about 50 ml to about 1000 ml, further wherein the second or thirdset of infusion containers comprise perfusion solution havingvinorelbine at a concentration ranging from about 0.01 mg/ml to 1.25mg/ml and volume of solution ranging from about 20 ml to about 100 ml;further wherein the perfusion solution has a pH ranging from about 3.8to 5.0.

According to one embodiment, the dose of vinorelbine for a particularindication is 30 mg/m² based on body surface area as the patientparameter. There is provided instructions to calculate the dose based onthe body surface area of the patient and select one or more perfusioncontainers of vinorelbine from different sets, to deliver the calculateddose within ±5% variance and is presented in table (43) below:

TABLE 43 Description of perfusion system of vinorelbine: First set ofPerfusion Second set of Top-up Third set of Top-up container Vinorelbineperfusion containers; perfusion containers; concentration - Vinorelbineconcentration - Vinorelbine concentration - 0.5 mg/ml 0.05 mg/ml 0.025mg/ml Total Target Volume of Dose delivered Volume of Dose deliveredVolume of Dose delivered % Variation** Dose to be perfusion fromperfusion top up from top-up top up from top-up Total dose fromdelivered BSA delivered container container container containercontainer container delivered dose Vs calculated (m²) (mg) D (ml) (a)(mg) (ml) (b) (mg) (ml) (c) (mg) (mg) (a + b + c) dose 1.4 42 80 40 40 20 0 42 0 1.5 45 90 45  0 0 0 0 45 0 1.6 48 90 45 40 2 40 1 48 0 1.7 51100 50  0 0 40 1 51 0 1.8 54 100 50 40 × 2 4 0 0 54 0 1.9 57 110 55 40 20 0 57 0 2.0 60 120 60  0 0 0 0 60 0 2.1 63 120 60 40 2 40 1 63 0 2.2 66130 65  0 0 40 1 66 0 2.3 69 130 65 40 × 2 4 0 0 69 0 2.4 72 140 70 40 20 0 72 0 2.5 75 150 75  0 0 0 0 75 0 2.6 78 150 75 40 2 40 1 78 0 **%Variation from delivered dose Vs calculated dose = [((a + b + c) − D]/D× 100

The containers of the perfusion system of Table (43) may be alphabeticalcoded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; vinorelbineconcen- vinorelbine concen- vinorelbine concen- tration 0.5 mg/mltration 0.05 mg/ml: tration 0.025 mg/ml: Volume of Volume of Volume ofperfusion Alpha- top up Alpha- top up Alpha- container betical containerbetical container betical (ml) code (ml) code (ml) code 80 A 40 I 40 J90 B 100 C 110 D 120 E 130 F 140 G 150 H

The perfusion system of Table (43) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.4 Connect one 80 ml container having analphabetical code A and one 40 ml container having an alphabetical codeI and infuse the full volume 1.5 Infuse the full volume from one 90 mlcontainer having an alphabetical code B 1.6 Connect one 90 ml containerhaving an alphabetical code B + one 40 ml container having analphabetical code I + one 40 ml container having an alphabetical code Jand infuse the full volume 1.7 Connect one 100 ml container having analphabetical code C and one 40 ml container having an alphabetical codeJ and infuse the full volume 1.8 Connect one 100 ml container having analphabetical code C and two 40 ml container having an alphabetical codeI and infuse the full volume 1.9 Connect one 110 ml container having analphabetical code D and one 40 ml container having an alphabetical codeI and infuse the full volume 2.0 Infuse the full volume from one 120 mlcontainer having an alphabetical code E 2.1 Connect one 120 ml containerhaving an alphabetical code E + one 40 ml container having analphabetical code I + one 40 ml container having an alphabetical code Jand infuse the full volume 2.2 Connect one 130 ml container having analphabetical code F and one 40 ml container having an alphabetical codeJ and infuse the full volume 2.3 Connect one 130 ml container having analphabetical code F and two 40 ml container having an alphabetical codeI and infuse the full volume 2.4 Connect one 140 ml container having analphabetical code G and one 40 ml container having an alphabetical codeI and infuse the full volume 2.5 Infuse the full volume from one 150 mlcontainer having an alphabetical code H 2.6 Connect one 150 ml containerhaving an alphabetical code H + one 40 ml container having analphabetical code I and one 40 ml container having an alphabetical codeJ and infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers todeliver the calculated target dose within ±5% of variation.

According to the present invention, the below embodiment providesperfusion system for administration of pemetrexed or itspharmaceutically acceptable salt such as pemetrexed disodiumheptahydrate. Table 44 below provides details of the perfusion systemhaving containers of first, second and/or third set with the ranges ofconcentration and volume of the solution per set.

TABLE 44 Perfusion system of pemetrexed: Second set Third set From setof First set of top up of top up container of of perfusion perfusionperfusion the perfusion system container container containerConcentration range 0.2-20.0 0.01-10.0  0.01-10.0  (mg/ml) Preferredconcentration range 1.0-11.0 0.02-5.0  0.01-5.0  (mg/ml) Volume range(ml)  25-1000 20-500 20-500 Preferred volume range 50-600 20-100 20-100(ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 45-47.

TABLE 45 Perfusion containers of the first set having Pemetrexed: Volumeof solution in bag Perfusion containers of first set (ml) 100 120 140170 200 250 Pemetrexed amount per bag 500 600 700 850 1000 1250 (mg) (ata concentration of 5.0 mg/ml)

TABLE 46 Perfusion containers of the second set having Pemetrexed:Perfusion containers of second set Volume of solution in bag (ml) 25 4050 60 Pemetrexed amount per bag 25 40 50 60 (mg) (at a concentration of1.0 mg/ml)

TABLE 47 Perfusion containers of the third set having Pemetrexed:Perfusion containers of third set Volume of solution in bag (ml) 20 2540 50 Pemetrexed amount per bag 10 12.5 20 25 (mg) (at a concentrationof 0.5 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis pemetrexed, the first set of infusion containers comprise perfusionsolution having pemetrexed at a concentration ranging from about 0.2mg/ml to 20.0 mg/ml and volume of solution ranging from about 25 ml toabout 1000 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having pemetrexed at aconcentration ranging from about 0.01 mg/ml to 10.0 mg/ml and volume ofsolution ranging from about 20 ml to about 100 ml, further wherein theperfusion solution has a pH ranging from about 6.0 to 8.0.

In one embodiment, the dose of pemetrexed for a particular indication is500 mg/m² based on patient's body surface area. There is providedinstructions for calculating the dose based on the body surface area andinstructions for selecting one or more perfusion containers ofpemetrexed from different sets, to deliver the calculated dose within±5% variance and is presented in table (48):

TABLE (48) Description of perfusion system of pemetrexed: First set ofPerfusion Second set of Top-up perfusion container Pemetrexedcontainers; Pemetrexed concentration - 5.0 mg/ml concentration 1.0 mg/mlTotal Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA delivered container container containercontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml)(b) (mg) (mg) (a + b + c) dose 1.2 600 100 500 50 × 2 100 600 0.0 1.3650 120 600 50 50 650 0.0 1.4 700 140 700  0 0 700 0.0 1.5 750 140 70050 50 750 0.0 1.6 800 140 700 50 × 2 100 800 0.0 1.7 850 170 850  0 0850 0.0 1.8 900 170 850 50 50 900 0.0 1.9 950 170 850 50 × 2 100 950 0.02.0 1000 200 1000  0 0 1000 0.0 2.1 1050 200 1000 50 50 1050 0.0 2.21100 200 1000 50 × 2 100 1100 0.0 2.3 1150 200 1000 50 × 2 100 1100 −4.32.4 1200 250 1250  0 0 1250 4.2 2.5 1250 250 1250  0 0 1250 0.0 2.6 1300250 1250 50 50 1300 0.0 **% Variation from delivered dose Vs calculateddose = [((a + b + c) − D]/D × 100

The containers of the perfusion system of Table (48) may be alphabeticalcoded as follows:

First set of Perfusion Second set of top-up perfusion containers;pemetrexed containers; pemetrexed concentration 5.0 mg/ml concentration1.0 mg/ml Volume of perfusion Alphabetical Volume of top up Alphabeticalcontainer (ml) code container (ml) code 100 A 50 G 120 B 140 C 170 D 200E 250 F

The perfusion system of Table (48) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Connect one 100 ml container having analphabetical code A and two 50 ml container having an alphabetical codeG and infuse the full volume 1.3 Connect one 120 ml container having analphabetical code B and one 50 ml container having an alphabetical codeG 1.4 Infuse the full volume from one 140 ml container having analphabetical code C 1.5 Connect from one 140 ml container having analphabetical code C and one 50 ml container having an alphabetical codeG and infuse the full volume 1.6 Connect one 140 ml container having analphabetical code C and two 50 ml container having an alphabetical codeG and infuse the full volume 1.7 Infuse the full volume from one 170 mlcontainer having an alphabetical code D 1.8 Connect one 170 ml containerhaving an alphabetical code D and one 50 ml container having analphabetical code G and infuse the full volume 1.9 Connect one 170 mlcontainer having an alphabetical code D and two 50 ml container havingan alphabetical code G and infuse the full volume 2.0 Infuse the fullvolume from one 200 ml container having an alphabetical code E 2.1Connect one 200 ml container having an alphabetical code E and one 50 mlcontainer having an alphabetical code G and infuse the full volume 2.2and 2.3 Connect one 200 ml container having an alphabetical code E andtwo 50 ml container having an alphabetical code G and infuse the fullvolume 2.4 and 2.5 Infuse the full volume from one 250 ml containerhaving an alphabetical code F 2.6 Connect one 250 ml container having analphabetical code F and one 50 ml container having an alphabetical codeG and infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers todeliver the calculated target dose within ±5% of variation.

According to the present invention, the below embodiment providesperfusion system for administration of gemcitabine or itspharmaceutically acceptable salt such as gemcitabine hydrochloride.Table 49 below provides details of the perfusion system havingcontainers of first, second and/or third set with the ranges ofconcentration and volume of the solution per set.

TABLE 49 Perfusion system of gemcitabine: Second set Third set From setof First set of top up of top up container of of perfusion perfusionperfusion the perfusion system container container containerConcentration range 0.1-15.0 0.005-7.5   0.005-7.5   (mg/ml) Preferredconcentration 1.0-10.0 0.01-5.0  0.01-5.0  range (mg/ml) Volume range(ml)  80-2000 20-800 20-800 Preferred volume range 100-1000 50-20050-200 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 50-52.

TABLE 50 Perfusion containers of first set having gemcitabine: Perfusioncontainers of first set Volume of solution in bag (ml) 100 120 150 180210 240 Gemcitabine amount per bag (mg) 1000 1200 1500 1800 2100 2400(at a concentration of 10 mg/ml)

TABLE 51 Perfusion containers of second set having gemcitabine:Perfusion containers of second set Volume of solution in bag (ml) 25 5080 100 Gemcitabine amount per bag 50 100 160 200 (mg) (at aconcentration of 2.0 mg/ml)

TABLE 52 Perfusion containers of the third set having gemcitabine:Perfusion containers of third set Volume of solution in bag (ml) 20 2550 100 Gemcitabine amount per bag 20 25 50 100 (mg) (at a concentrationof 1.0 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis gemcitabine, the first set of infusion containers comprise perfusionsolution having gemcitabine at a concentration ranging from about 0.1mg/ml to 15.0 mg/ml and volume of solution ranging from about 25 ml toabout 2000 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having gemcitabine at aconcentration ranging from about 0.005 mg/ml to 7.5 mg/ml and volume ofsolution ranging from about 20 ml to about 100 ml, further wherein theperfusion solution has a pH ranging from about 6.0 to 8.0.

According to one embodiment, the dose of gemcitabine for a particularindication is 1000 mg/m² based on body surface area. There is providedinstructions for calculating the dose and instructions for selecting oneor more perfusion containers of gemcitabine from different sets, todeliver the calculated dose within ±5% variance and is presented intable (53) below:

TABLE (53) Description of perfusion system of gemcitabine: First set ofPerfusion Second set of Top-up Third Set of Top-up container Gemcitabineperfusion containers; perfusion containers; concentration Gemcitabineconcentration Gemcitabine concentration 10 mg/ml 2 mg/ml: 1 mg/ml TotalTarget Volume of Dose delivered Volume of Dose delivered Volume of Dosedelivered % Variation** Dose to be perfusion from perfusion top up fromtop-up top up from top-up Total dose from delivered BSA deliveredcontainer container container container container container delivereddose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml) (b) (mg) (ml) (c) (mg)(mg) (a + b + c) dose 1.2 1200 100 1000 100 200 0 0 1200 0.0 1.3 1300120 1200 0 0 100 100 1300 0.0 1.4 1400 120 1200 100 200 0 0 1400 0.0 1.51500 120 1200 100 200 100 100 1500 0.0 1.6 1600 150 1500 0 0 100 1001600 0.0 1.7 1700 150 1500 100 200 0 0 1700 0.0 1.8 1800 150 1500 100200 100 100 1800 0.0 1.9 1900 180 1800 0 0 100 100 1900 0.0 2.0 2000 1801800 100 200 0 0 2000 0.0 2.1 2100 210 2100 0 0 0 0 2100 0.0 2.2 2200210 2100 0 0 100 100 2200 0.0 2.3 2300 210 2100 100 200 0 0 2300 0.0 2.42400 210 2100 100 200 100 100 2400 0.0 2.5 2500 240 2400 0 0 100 1002500 0.0 2.6 2600 240 2400 100 200 0 0 2600 0.0 **% Variation fromdelivered dose Vs calculated dose = [((a + b + c) − D]/D × 100

The containers of the perfusion system of Table (53) may bealphabetically coded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; gemcitabineconcen- gemcitabine concen- gemcitabine concen- tration 10 mg/ml tration2 mg/ml tration 1 mg/ml: Volume of Volume of Volume of perfusion Alpha-top up Alpha- top up Alpha- container betical container beticalcontainer betical (ml) code (ml) code (ml) code 100 A 100 G 100 H 120 B150 C 180 D 210 E 240 F

The perfusion system of Table (53) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Connect one 100 ml container having analphabetical code A and one 100 ml container having an alphabetical codeG and infuse the full volume 1.3 Connect one 100 ml container having analphabetical code A and one 100 ml container having an alphabetical codeH and infuse the full volume 1.4 Connect one 120 ml container having analphabetical code B and one 100 ml container having an alphabetical codeG and infuse the full volume 1.5 Connect one 120 ml container having analphabetical code B + one 100 ml container having an alphabetical codeG + one 100 ml container having an alphabetical code H and infuse thefull volume 1.6 Connect one 150 ml container having an alphabetical codeC and one 100 ml container having an alphabetical code H and infuse thefull volume 1.7 Connect one 150 ml container having an alphabetical codeC and one 100 ml container having an alphabetical code G and infuse thefull volume 1.8 Connect one 150 ml container having an alphabetical codeC + one 100 ml container having an alphabetical code G + one 100 mlcontainer having an alphabetical code H and infuse the full volume 1.9Connect one 180 ml container having an alphabetical code D + one 100 mlcontainer having an alphabetical code H and infuse the full volume 2.0Connect one 180 ml container having an alphabetical code D and one 100ml container having an alphabetical code G and infuse the full volume2.1 Infuse the full volume from one 210 ml container having analphabetical code E 2.2 Connect one 210 ml container having analphabetical code E and one 100 ml container having an alphabetical codeH and infuse the full volume 2.3 Connect one 210 ml container having analphabetical code E and one 100 ml container having an alphabetical codeG and infuse the full volume 2.4 Connect one 210 ml container having analphabetical code E + one 100 ml container having an alphabetical codeG + one 100 ml container having an alphabetical code H and infuse thefull volume 2.5 Connect one 240 ml container having an alphabetical codeF + one 100 ml container having an alphabetical code H and infuse thefull volume 2.6 Connect one 240 ml container having an alphabetical codeF + one 100 ml container having an alphabetical code G and infuse thefull volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers todeliver the calculated target dose within ±5% of variation.

According to yet another embodiment for gemcitabine at a dose is 1000mg/m² in accordance with body surface area as the patient parameter, thetable (54) below provides instructions for calculation of the dose andinstructions for selecting one or more perfusion containers ofgemcitabine from different sets, to deliver the calculated dose within±5% variance:

(54): Description of perfusion system of gemcitabine:

First set of Perfusion Second set of Top-up Third Set of Top-upcontainer Gemcitabine perfusion containers; perfusion containers;concentration Gemcitabine concentration Gemcitabin econcentration 10mg/ml 4 mg/ml: 4 mg/ml Total Target Volume of Dose delivered Volume ofDose delivered Volume of Dose delivered % Variation** Dose to beperfusion from perfusion top up from top-up top up from top-up Totaldose from delivered BSA delivered container container containercontainer container container delivered dose Vs calculated (m²) (mg) D(ml) (a) (mg) (ml) (b) (mg) (ml) (c) (mg) (mg) (a + b + c) dose 1.2 1200100 1000 50 200 0 0 1200 0.0 1.3 1300 120 1200 0 0 25 100 1300 0.0 1.41400 120 1200 50 200 0 0 1400 0.0 1.5 1500 120 1200 50 200 25 100 15000.0 1.6 1600 150 1500 0 0 25 100 1600 0.0 1.7 1700 150 1500 50 200 0 01700 0.0 1.8 1800 150 1500 50 200 25 100 1800 0.0 1.9 1900 180 1800 0 025 100 1900 0.0 2.0 2000 180 1800 50 200 0 0 2000 0.0 2.1 2100 210 21000 0 0 0 2100 0.0 2.2 2200 210 2100 0 0 25 100 2200 0.0 2.3 2300 210 210050 200 0 0 2300 0.0 2.4 2400 210 2100 50 200 25 100 2400 0.0 2.5 2500240 2400 0 0 25 100 2500 0.0 2.6 2600 240 2400 50 200 0 0 2600 0.0 **%Variation from delivered dose Vs calculated dose = [((a + b + c) − D]/D× 100

The containers of the perfusion system of Table (54) may be alphabeticalcoded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; gemcitabineconcen- vinblastine concen- vinblastine concen- tration 10 mg/ml tration4 mg/ml tration 4 mg/ml: Volume of Volume of Volume of perfusion Alpha-top up Alpha- top up Alpha- container betical container beticalcontainer betical (ml) code (ml) code (ml) code 100 A 50 I 25 J 120 B150 C 180 D 210 E 240 F

The perfusion system of Table (54) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Connect one 100 ml container having analphabetical code A and one 50 ml container having an alphabetical codeI and infuse the full volume 1.3 Connect one 120 ml container having analphabetical code B + one 25 ml container having an alphabetical code Jand infuse the full volume 1.4 Connect one 120 ml container having analphabetical code B + one 50 ml container having an alphabetical code Iand infuse the full volume 1.5 Connect one 120 ml container having analphabetical code B + one 50 ml container having an alphabetical codeI + one 25 ml container having an alphabetical code J and infuse thefull volume 1.6 Connect one 150 ml container having an alphabetical codeC + one 25 ml container having an alphabetical code J and infuse thefull volume 1.7 Connect one 150 ml container having an alphabetical codeC + one 50 ml container having an alphabetical code I and infuse thefull volume 1.8 Connect one 150 ml container having an alphabetical codeC + one 50 ml container having an alphabetical code I + one 25 mlcontainer having an alphabetical code J and infuse the full volume 1.9Connect one 180 ml container having an alphabetical code D + one 25 mlcontainer having an alphabetical code J and infuse the full volume 2.0Connect one 180 ml container having an alphabetical code D + one 50 mlcontainer having an alphabetical code I and infuse the full volume 2.1Infuse the full volume from one 210 ml container having an alphabeticalcode E 2.2 Connect one 210 ml container having an alphabetical code E +one 25 ml container having an alphabetical code J and infuse the fullvolume 2.3 Connect one 210 ml container having an alphabetical code E +one 50 ml container having an alphabetical code I and infuse the fullvolume 2.4 Connect one 210 ml container having an alphabetical code E +one 50 ml container having an alphabetical code I + one 25 ml containerhaving an alphabetical code J and infuse the full volume 2.5 Connect one240 ml container having an alphabetical code F + one 25 ml containerhaving an alphabetical code J and infuse the full volume 2.6 Connect one240 ml container having an alphabetical code F + one 50 ml containerhaving an alphabetical code I and infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers todeliver the calculated target dose within ±5% of variation.

According to yet another embodiment for gemcitabine, the dose for aparticular indication is 1000 mg/m² in accordance with body surface areaas the patient parameter. The table (55) below provides instruction forcalculation of total dose to be delivered to a patient based on the bodysurface area and instructions for selecting one or more perfusioncontainers of gemcitabine from different sets, to deliver the calculateddose within ±5% variance:

TABLE 55 Description of perfusion system of gemcitabine: First set ofPerfusion Second set of Top-up perfusion container Gemcitabinecontainers; Gemcitabine concentration 10 mg/ml concentration 10 mg/ml:Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA delivered container container containercontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml)(b) (mg) (mg) (a + b) dose 1.2 1200 120 1200 0 0 1200.00 0.00 1.3 1300130 1300 0 0 1300.00 0.00 1.4 1400 140 1400 0 0 1400.00 0.00 1.5 1500150 1500 0 0 1500.00 0.00 1.6 1600 160 1600 0 0 1600.00 0.00 1.7 1700170 1700 0 0 1700.00 0.00 1.8 1800 180 1800 0 0 1800.00 0.00 1.9 1900190 1900 0 0 1900.00 0.00 2 2000 200 2000 0 0 2000.00 0.00 2.1 2100 2002000 0 0 2000.00 −4.76 2.2 2200 220 2200 0 0 2200.00 0.00 2.3 2300 2202200 0 0 2200.00 −4.35 2.4 2400 120 1200 120 1200 2400.00 0.00 2.5 2500130 1300 120 1200 2500.00 0.00 2.6 2600 130 1300 130 1300 2600.00 0.00**% Variation from delivered dose Vs calculated dose = [((a + b + c) −D]/D × 100

The containers of the perfusion system of Table (55) may be alphabeticalcoded as follows:

First set of Second set of top-up Third set of top-up Perfusioncontainers; perfusion containers; perfusion containers; gemcitabineconcen- vinblastine concen- vinblastine concen- tration 10 mg/ml tration4 mg/ml tration 4 mg/ml: Volume of Volume of Volume of perfusion Alpha-top up Alpha- top up Alpha- container betical container beticalcontainer betical (ml) code (ml) code (ml) code 120 B 120 B 130 K 130 K140 L 150 C 160 M 170 N 180 D 190 O 200 P 220 Q

The perfusion system of Table (55) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Infuse the full volume from one 120 mlcontainer having an alphabetical code B 1.3 Infuse the full volume fromone 130 ml container having an alphabetical code K 1.4 Infuse the fullvolume from one 140 ml container having an alphabetical code L 1.5Infuse the full volume from one 150 ml container having an alphabeticalcode C 1.6 Infuse the full volume from one 160 ml container having analphabetical code M 1.7 Infuse the full volume from one 170 ml containerhaving an alphabetical code N 1.8 Infuse the full volume from one 180 mlcontainer having an alphabetical code D 1.9 Infuse the full volume fromone 190 ml container having an alphabetical code O 2.0 and 2.1 Infusethe full volume from one 200 ml container having an alphabetical code P2.2 and 2.3 Infuse the full volume from one 220 ml container having analphabetical code Q 2.4 Connect two 120 ml container having analphabetical code B and infuse the full volume 2.5 Connect one 130 mlcontainer having an alphabetical code K + one 120 ml container having analphabetical code B and infuse the full volume 2.6 Connect two 130 mlcontainer having an alphabetical code K and infuse the full volume

According to yet another embodiment for gemcitabine, the dose for aparticular indication is 1250 mg/m² in accordance with body surface areaas the patient parameter. The table (56) below provides instruction forcalculation of total dose to be delivered to a patient based on the bodysurface area and instructions for selecting one or more perfusioncontainers of gemcitabine from different sets, to deliver the calculateddose within ±5% variance:

TABLE 56 Description of perfusion system of gemcitabine: First set ofPerfusion Second set of Top-up perfusion container Gemcitabinecontainers; Gemcitabine concentration 10 mg/ml concentration 10 mg/ml:Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA delivered container container containercontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml)(b) (mg) (mg) (a + b) dose 1.2 1500 150 1500 0 0 1500.00 0.00 1.3 1625160 1600 0 0 1600.00 −1.54 1.4 1750 170 1700 0 0 1700.00 −2.86 1.5 1875190 1900 0 0 1900.00 1.33 1.6 2000 200 2000 0 0 2000.00 0.00 1.7 2125220 2200 0 0 2200.00 3.53 1.8 2250 220 2200 0 0 2200.00 −2.22 1.9 2375120 1200 120 1200 2400.00 1.05 2 2500 130 1300 120 1200 2500.00 0.00 2.12625 130 1300 130 1300 2600.00 −0.95 2.2 2750 150 1500 120 1200 2700.00−1.82 2.3 2875 140 1400 140 1400 2800.00 −2.61 2.4 3000 150 1500 1501500 3000.00 0.00 2.5 3125 190 1900 120 1200 3100.00 −0.80 2.6 3250 1601600 160 1600 3200.00 −1.54

The containers of the perfusion system of Table (56) may bealphabetically coded as follows:

First set of Perfusion containers; gemcitabine concentration 10 mg/mlVolume of perfusion container (ml) Alphabetical code 120 B 130 K 140 L150 C 160 M 170 N 190 O 200 P 220 Q

The perfusion system of Table (56) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.2 Infuse the full volume from one 150 mlcontainer having an alphabetical code C 1.3 Infuse the full volume fromone 160 ml container having an alphabetical code M 1.4 Infuse the fullvolume from one 170 ml container having an alphabetical code N 1.5Infuse the full volume from one 190 ml container having an alphabeticalcode O 1.6 Infuse the full volume from one 200 ml container having analphabetical code P 1.7 and 1.8 Infuse the full volume from one 220 mlcontainer having an alphabetical code Q 1.9 Infuse the full volume fromtwo 120 ml container having an alphabetical code B 2.0 Connect one 130ml container having an alphabetical code K + one 120 ml container havingan alphabetical code B and infuse the full volume 2.1 Infuse the fullvolume from two 130 ml container having an alphabetical code K 2.2Connect one 150 ml container having an alphabetical code C + one 120 mlcontainer having an alphabetical code B and infuse the full volume 2.3Infuse the full volume from two 140 ml container having an alphabeticalcode L 2.4 Infuse the full volume from two 150 ml container having analphabetical code C 2.5 Connect one 190 ml container having analphabetical code O + one 120 ml container having an alphabetical code Band infuse the full volume 2.6 Infuse the full volume from two 160 mlcontainer having an alphabetical code M

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers todeliver the calculated target dose within ±5% of variation.

According to the present invention, the below embodiment providesperfusion system for administration of azacitidine or itspharmaceutically acceptable salt. Table 57 below provides details of theperfusion system having containers of first, second and/or third setwith the ranges of concentration and volume of the solution per set.

TABLE 57 Perfusion system of azacitidine: From set of container of theperfusion system Second set Third set First set of top up of top up ofperfusion perfusion perfusion container container containerConcentration range 0.07-5.0  0.05-0.5  0.05-0.5  (mg/ml) Preferredconcentration 0.5-2.5  0.1-0.2  0.05-0.07  range (mg/ml) Volume range(ml) 50-500 50-250 50-100 Preferred volume range 50-100 50-100 50-100(ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 58-60

TABLE 58 Perfusion containers of the first set having Azacitidine:Perfusion containers of first set Volume of solution in bag (ml) 60 7080 90 100 120 200 AZACITIDINE amount per bag (mg) 30 35 40 45 50 60 100(at a concentration of 0.5 mg/ml) AZACITIDINE amount per bag (mg) 60 7080 90 100 120 200 (at a concentration of 1.0 mg/ml) AZACITIDINE amountper bag (mg) 90 105 120 135 150 180 300 (at a concentration of 1.5mg/ml) AZACITIDINE amount per bag (mg) 150 175 200 225 250 300 500 (at aconcentration of 2.5 mg/ml)

TABLE 59 Perfusion containers of the second set having Azacitidine:Perfusion containers of second set Volume of solution in bag (ml) 25 4050 60 100 Azacitidine amount per bag 5.0 8.0 10.0 12.0 20.0 (mg) (at aconcentration of 0.2 mg/ml)

TABLE 60 Perfusion containers of the third set having Azacitidine:Perfusion containers of third set Volume of solution in bag (ml) 20 2540 Azacitidine amount per bag 1.0 1.25 2.0 (mg) (at a concentration of0.05 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis Azacitidine, the first set of infusion containers comprise perfusionsolution having Azacitidine at a concentration ranging from about 0.07mg/ml to 5.0 mg/ml and volume of solution ranging from about 40 ml toabout 1000 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having Azacitidine at aconcentration ranging from about 0.05 mg/ml to 0.5 mg/ml and volume ofsolution ranging from about 20 ml to about 100 ml.

According to one embodiment, the dose of Azacitidine for a particularindication is 100 mg/m² based on body surface area as the patientparameter. There is provided instructions for calculating the total doseto be delivered to a patient based on the body surface area andinstructions for selecting one or more perfusion containers ofAzacitidine from different sets, to deliver the calculated dose within±5% variance and is presented in table (61)

TABLE (61) Description of perfusion system of Azacitidine: First set ofPerfusion Second set of Top-up perfusion container; Azacitidinecontainers- Azacitidine concentration- 2.5 mg/ml concentration - 0.2mg/ml Total Target Volume of Dose delivered Volume of Dose deliveredTotal dose % Variation** Dose to be perfusion from perfusion top up fromtop-up delivered from delivered BSA delivered container containercontainer container (mg) dose Vs calculated (m²) D (mg) (ml) (a) (mg)(ml) (b) (mg) (a + b) dose % 1.4 140 55 137.5 0 0 137.5 −1.8 1.5 150 55137.5 50 10 147.5 −1.7 1.6 160 65 162.5 0 0 162.5 1.6 1.7 170 65 162.550 10 172.5 1.5 1.8 180 65 162.5 50 10 172.5 −4.2 1.9 190 75 187.5 0 0187.5 −1.3 2 200 80 200 0 0 200 0.0 2.1 210 80 200 50 10 210 0.0 2.2 22080 200 50 10 210 −4.5 2.3 230 90 225 0 0 225 −2.2 2.4 240 90 225 50 10235 −2.1 **% Variation from delivered dose Vs calculated dose = [((a +b) − D]/D × 100

The containers of the perfusion system of Table (61) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containers;azacitidine containers; azacitidine concentration 2.5 mg/mlconcentration 0.2 mg/ml Volume of perfusion Alphabetical Volume of topup Alphabetical container (ml) code container (ml) code 55 A 50 F 65 B75 C 80 D 90 E

The perfusion system of Table (61) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.4 Infuse the full volume from one 55 mlcontainer having an alphabetical code A 1.5 Connect one 55 ml containerhaving an alphabetical code A with one 50 ml container having analphabetical code F and Infuse the full volume 1.6 Infuse the fullvolume from one 65 ml container having an alphabetical code B 1.8Connect one 65 ml container having an alphabetical code B with one 50 mlcontainer having an alphabetical code F and Infuse the full volume 1.9Infuse the full volume from one 75 ml container having an alphabeticalcode C 2.0 Infuse the full volume from one 80 ml container having analphabetical code D 2.1 and 2.2 Connect one 80 ml container having analphabetical code D with one 50 ml container having an alphabetical codeF and Infuse the full volume 2.3 Infuse the full volume from one 90 mlcontainer having an alphabetical code E 2.4 Connect one 90 ml containerhaving an alphabetical code E with one 50 ml container having analphabetical code F and Infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers andfull volume is infused to deliver the calculated target dose within ±5%of variation.

According to the present invention, the below embodiment providesperfusion system for administration of arsenic trioxide or itspharmaceutically acceptable salt. Table 62 below provides details of theperfusion system having containers of first, second and/or third setwith the ranges of concentration and volume of the solution per set.

TABLE 62 Perfusion system of arsenic trioxide: From set of container ofthe perfusion system Second set Third set First set of top up of top upof perfusion perfusion perfusion container container containerConcentration range 0.03-0.2 0.03-0.07 0.03-0.07 (mg/ml) Preferredconcentration 0.05-0.1 0.03-0.05 0.03-0.05 range (mg/ml) Volume range(ml)  50-500  50-250  25-200 Preferred volume range  100-250  50-100 50-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 63-65.

TABLE 63 Perfusion containers of the first set having arsenic trioxide:Perfusion containers of first set Volume of solution in bag (ml) 100 110140 150 190 200 230 Arsenic trioxide amount per bag (mg) 7 7.7 9.8 10.513.3 14.0 16.1 (at a concentration of 0.07 mg/ml)

TABLE 64 Perfusion containers of the second set having arsenic trioxide:Perfusion containers of second set Volume of solution in bag (ml) 50 75100 Arsenic trioxide amount per bag 1.5 2.25 3.0 (mg) (at aconcentration of 0.03 mg/ml)

TABLE 65 Perfusion containers of the third set having arsenic trioxide:Perfusion containers of third set Volume of solution in bag (ml) 50 80Arsenic trioxide amount per bag 1.0 1.6 (mg) (at a concentration of 0.02mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis Arsenic trioxide, the first set of infusion containers compriseperfusion solution having Arsenic trioxide at a concentration rangingfrom about 0.03 mg/ml to 0.2 mg/ml and volume of solution ranging fromabout 50 ml to about 500 ml, further wherein the second or third set ofinfusion containers comprise perfusion solution having Arsenic trioxideat a concentration ranging from about 0.03-0.07 mg/ml and volume ofsolution ranging from about 20 ml to about 100 ml.

According to one embodiment, the dose of Arsenic trioxide for aparticular indication is 0.15 mg/Kg based on body weight as the patientparameter. There is provided instructions for calculating the total doseto be delivered to a patient based on the body surface area andinstructions for selecting one or more perfusion containers of Arsenictrioxide from different sets, to deliver the calculated dose within ±5%variance and is presented in table (66):

TABLE 66 Description of perfusion system of Arsenic trioxide: First setof perfusion Second set of Top-up perfusion container; Arsenic Trioxidecontainers; Arsenic Trioxide concentration - 0.07 mg/mL concentration -0.03 mg/mL Total Target Volume of Dose delivered Volume of Dosedelivered % Variation** Dose to be perfusion from perfusion top up fromtop-up Total Dose from delivered Body delivered container containercontainer container delivered dose Vs. calculated Weight D (mg) (ml) (a)(mg) (ml) (b) (mg) a + b (mg) dose 50 7.50 110 7.7 0 0 7.7 2.7 55 8.25100 7 50 1.5 8.5 3.0 60 9.00 110 7.7 50 1.5 9.2 2.2 65 9.75 140 9.8 0 09.8 0.5 70 10.50 150 10.5 0 0 10.5 0.0 75 11.25 140 9.8 50 1.5 11.3 0.480 12.00 150 10.5 50 1.5 12.0 0.0 85 12.75 190 13.3 0 0 13.3 4.3 9013.50 190 13.3 0 0 13.3 −1.5 95 14.25 190 13.3 50 1.5 14.8 3.7 100 15.00190 13.3 50 1.5 14.8 −1.3 105 15.75 230 16.1 0 0 16.1 2.2 110 16.50 23016.1 0 0 16.1 −2.4 115 17.25 230 16.1 50 1.5 17.6 2.0 120 18.00 230 16.150 1.5 17.6 −2.2 **% Variation from delivered dose Vs calculated dose =[((a + b) − D]/D × 100

The containers of the perfusion system of Table (66) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containers;Arsenic Trioxide containers; Arsenic Trioxide concentration 0.07 mg/mlconcentration 0.03 mg/ml Volume of perfusion Alphabetical Volume of topup Alphabetical container (ml) code container (ml) code 100 A 50 G 110 B140 C 150 D 190 E 230 F

The perfusion system of Table (66) is accompanied by suitableinstructions for example as below:

Body Weight Instructions 50 Infuse the full volume from one 110 mlcontainer having an alphabetical code B 55 Connect one 100 ml containerhaving an alphabetical code A with one 50 ml container having analphabetical code G and Infuse the full volume 60 Connect one 110 mlcontainer having an alphabetical code B with one 50 ml container havingan alphabetical code G and Infuse the full volume 65 Infuse the fullvolume from one 140 ml container having an alphabetical code C 70 Infusethe full volume from one 150 ml container having an alphabetical code D75 Connect one 140 ml container having an alphabetical code C with one50 ml container having an alphabetical code G and Infuse the full volume80 Connect one 150 ml container having an alphabetical code D with one50 ml container having an alphabetical code G and Infuse the full volume85 and 90 Infuse the full volume from one 190 ml container having analphabetical code E  95 and 100 Connect one 190 ml container having analphabetical code E with one 50 ml container having an alphabetical codeG and Infuse the full volume 105 and 110 Infuse the full volume from one230 ml container having an alphabetical code F 115 and 120 Connect one230 ml container having an alphabetical code F with one 50 ml containerhaving an alphabetical code G and Infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers andfull volume is infused to deliver the calculated target dose within ±5%of variation.

According to the present invention, the below embodiment providesperfusion system for administration of fluorouracil or itspharmaceutically acceptable salt. Table 67 below provides details of theperfusion system having containers of first, second and/or third setwith the ranges of concentration and volume of the solution per set.

TABLE 67 Perfusion system of fluorouracil: From set of container of theperfusion system Second set Third set First set of top up of top up ofperfusion perfusion perfusion container container containerConcentration range 0.50 to 6.0 0.1-1.0 0.1-1.0 (mg/ml) Preferredconcentration 0.85 to 2.6 1.0 0.5 range (mg/ml) Volume range (ml)50-1000 mL 25-100 mL 20-100 mL Preferred volume range 200-500 mL    50mL    50 mL (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 68-70.

TABLE 68 Other Perfusion containers of the first set having 0.85 mg/mlfluorouracil: Perfusion containers of first set Volume of solution inbag (ml) 200 250 300 350 400 450 500 Fluorouracil amount per bag (mg)170 212.5 255 297.5 340 382.5 425 (at a concentration of 0.85 mg/ml)

TABLE 69 Perfusion containers of the second set having fluorouracil:Perfusion containers of second set Volume of solution in bag (ml) 25 5075 100 Fluorouracil amount per bag 12.5 25 37.5 50 (mg) (at aconcentration of 0.5 mg/ml)

TABLE 70 Perfusion containers of the third set having fluorouracil:Perfusion containers of third set Volume of solution in bag (ml) 20 5075 100 Fluorouracil amount per bag 5 12.5 18.75 25 (mg) (at aconcentration of 0.25 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis Fluorouracil, the first set of infusion containers comprise perfusionsolution having Fluorouracil at a concentration ranging from about 0.5mg/ml to 6.0 mg/ml and volume of solution ranging from about 50 ml toabout 1000 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having Fluorouracil at aconcentration ranging from about 0.1-1.0 mg/ml and volume of solutionranging from about 20 ml to about 100 ml.

According to one embodiment, the dose of Fluorouracil for a particularindication is 5 mg/Kg based on body weight as the patient parameter.There is provided instructions for calculating the total dose to bedelivered to a patient based on the body weight and instructions forselecting one or more perfusion containers of Fluorouracil fromdifferent sets, to deliver the calculated dose within ±5% variance andis presented in table (71):

TABLE 71 Description of perfusion system of Fluorouracil: First set ofPerfusion Second set of Top-up perfusion container; Fluorouracilcontainer; Fluorouracil concentration 0.85 mg/ml concentration 0.5mg/ml: Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Body Dose to be perfusion from perfusion top up from top-upTotal dose from delivered Weight delivered container container containercontainer delivered dose Vs calculated kg (mg) D (ml) (a) (mg) (ml) (b)(mg) (mg) (a + b) dose 50 250 300 255 0 0 255 2.0 55 275 300 255 50 25280 1.8 60 300 300 255 100 50 305 1.7 65 325 400 340 0 0 340 4.6 70 350400 340 0 0 340 −2.9 75 375 400 340 50 25 365 −2.7 80 400 400 340 100 50390 −2.5 85 425 500 425 0 0 425 0.0 90 450 500 425 50 25 450 0.0 95 475500 425 100 50 475 0.0 100 500 600 510 0 0 510 2.0 **% Variation fromdelivered dose Vs calculated dose = [((a + b) − D]/D × 100

The containers of the perfusion system of Table (71) may bealphabetically coded as follows:

First set of Perfusion Second set of top-up perfusion containers;Fluorouracil containers; Fluorouracil concentration 0.85 mg/mlconcentration 0.5 mg/ml Volume of perfusion Alphabetical Volume of topup Alphabetical container (ml) code container (ml) code 300 A 50 E 400 B100 F 500 C 600 D

The perfusion system of Table (71) is accompanied by suitableinstructions for example as below:

Body Weight Instructions 50 Infuse the full volume from one 300 mlcontainer having an alphabetical code A 55 Connect one 300 ml containerhaving an alphabetical code A with one 50 ml container having analphabetical code E and Infuse the full volume 60 Connect one 300 mlcontainer having an alphabetical code A with one 100 ml container havingan alphabetical code F and Infuse the full volume 65 and 70 Infuse thefull volume from one 400 ml container having an alphabetical code B 75Connect one 400 ml container having an alphabetical code B with one 50ml container having an alphabetical code E and Infuse the full volume 80Connect one 400 ml container having an alphabetical code B with one 100ml container having an alphabetical code F and Infuse the full volume 85Infuse the full volume from one 500 ml container having an alphabeticalcode C 90 Connect one 500 ml container having an alphabetical code Cwith one 50 ml container having an alphabetical code E and Infuse thefull volume 95 Connect one 500 ml container having an alphabetical codeC with one 100 ml container having an alphabetical code F and Infuse thefull volume 100  Infuse the full volume from one 600 ml container havingan alphabetical code D

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers andfull volume is infused to deliver the calculated target dose within ±5%of variation.

According to the present invention, the below embodiment providesperfusion system for administration of paclitaxel or itspharmaceutically acceptable salt. Table 72 below provides details of theperfusion system having containers of first, second and/or third setwith the ranges of concentration and volume of the solution per set.

TABLE 72 Perfusion system of paclitaxel: From set of container of theperfusion system Second set Third set First set of top up of top up ofperfusion perfusion perfusion container container containerConcentration range 0.1 to 2   0.1 to 2   0.1 to 2   (mg/ml) Preferredconcentration 0.3 to 1.2 0.3 to 1.2 0.3 to 1.2 range (mg/ml) Volumerange (ml) 40-600 50-150 50-150 Preferred volume range 50-500 50-10050-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 73-75.

TABLE 73 Perfusion containers of the first set having paclitaxel:Perfusion containers of first set Volume of solution in bag (ml) 120 130140 160 175 205 245 290 350 Paclitaxel amount per bag (mg) 60 65 70 8087.5 102.5 122.5 145 175 (at a concentration of 0.5 mg/ml)

TABLE 74 Perfusion containers of the second set having paclitaxel:Perfusion containers of second set Volume of solution in bag (ml) 50 75100 150 Paclitaxel amount per bag 20 30 40 60 (mg) (at a concentrationof 0.4 mg/ml)

TABLE 75 Perfusion containers of the third set having paclitaxel:Perfusion containers of third set Volume of solution in bag (ml) 50 75100 150 Paclitaxel amount per bag 12.5 18.75 25 37.5 (mg) (at aconcentration of 0.25 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis Paclitaxel, the first set of infusion containers comprise perfusionsolution having Paclitaxel at a concentration ranging from about 0.1mg/ml to 2.0 mg/ml and volume of solution ranging from about 40 ml toabout 600 ml, further wherein the second or third set of infusioncontainers comprise perfusion solution having Paclitaxel at aconcentration ranging from about 0.1-2.0 mg/ml and volume of solutionranging from about 25 ml to about 150 ml.

According to one embodiment, the dose of Paclitaxel for a particularindication is 50 mg/m² based on body surface area as the patientparameter. There is provided instructions for calculating the total doseto be delivered to a patient based on the body surface area andinstructions for selecting one or more perfusion containers ofPaclitaxel from different sets, to deliver the calculated dose within±5% variance and is presented in table (76):

TABLE (76) Description of perfusion system of Paclitaxel: First set ofPerfusion Second set of top-up perfusion container Paclitaxelcontainers; Paclitaxel concentration 0.5 mg/ml concentration 0.4 mg/ml:Total Target Volume of Dose delivered Volume of Dose delivered %Variation** Dose to be perfusion from perfusion top up from top-up Totaldose from delivered BSA delivered container container containercontainer delivered dose Vs calculated (m²) (mg) D (ml) (a) (mg) (ml)(b) (mg) (mg) (a + b) dose 1.4 70.0 145.0 72.5 0 0.0 72.5 3.6 1.5 75.0145.0 72.5 0 0.0 72.5 −3.3 1.6 80.0 160.0 80.0 0 0.0 80.0 0.0 1.7 85.0175.0 87.5 0 0.0 87.5 2.9 1.8 90.0 175.0 87.5 0 0.0 87.5 −2.8 1.9 95.0145.0 72.5 50.0 20.0 92.5 −2.6 2 100.0 160.0 80.0 50.0 20.0 100 0 2.1105.0 210.0 105.0 0 0.0 105 0 2.2 110.0 175.0 87.5 50.0 20.0 107.5 2.32.3 115.0 200.0 100 50.0 20.0 120 4.3 2.4 120.0 245.0 122.5 0 0.0 122.52.1 **% Variation from delivered dose Vs calculated dose = [((a + b) −D]/D × 100

The containers of the perfusion system of Table (76) may be alphabeticalcoded as follows:

First set of Perfusion Second set of top-up perfusion containers;paclitaxel containers; paclitaxel concentration 0.5 mg/ml concentration0.4 mg/ml Volume of perfusion Alphabetical Volume of top up Alphabeticalcontainer (ml) code container (ml) code 145 A 50 G 160 B 175 C 200 D 210E 245 F

The perfusion system of Table (76) is accompanied by suitableinstructions for example as below:

BSA (m²) Instructions 1.4 and 1.5 Infuse the full volume from one 145 mlcontainer having an alphabetical code A 1.6 Infuse the full volume fromone 160 ml container having an alphabetical code B 1.7 and 1.8 Infusethe full volume from one 175 ml container having an alphabetical code C1.9 Connect one 145 ml container having an alphabetical code A with one50 ml container having an alphabetical code G and Infuse the full volume2.0 Connect one 160 ml container with B with one 50 ml container with Gand Infuse the full volume 2.1 Infuse the full volume from one 210 mlcontainer with E 2.2 Connect one 175 ml container with C with one 50 mlcontainer with G and Infuse the full volume 2.3 Connect one 200 mlcontainer with D with one 50 ml container with G and Infuse the fullvolume 2.4 Infuse the full volume from one 245 ml container with F

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers andfull volume is infused to deliver the calculated target dose within ±5%of variation.

According to the present invention, the below embodiment providesperfusion system for administration of cyclophosphamide or itspharmaceutically acceptable salt. Table 77 below provides details of theperfusion system having containers of first, second and/or third setwith the ranges of concentration and volume of the solution per set.

TABLE 77 Perfusion system of cyclophosphamide: From set of container ofthe perfusion system Second set Third set First set of top up of top upof perfusion perfusion perfusion container container containerConcentration range  5-30 1-15 1-15 (mg/ml) Preferred concentration15-25 5-10 1-10 range (mg/ml) Volume range (ml)  100-1000 30-150 30-150Preferred volume range 100-500 50-100 50-100 (ml)

The perfusion system may comprise one or more perfusion containers inthe first set and one or more perfusion containers in the second and/orthird set. The containers in different sets according to one preferredembodiment of the present invention are given below in Tables 78-80.

TABLE 78 Perfusion containers of the first set having cyclophosphamide:Perfusion containers of first set Volume of solution in bag (ml) 100 115125 135 145 160 175 200 Cyclophosphamide amount per bag (mg) 2000 23002500 2700 2900 3200 3500 4000 (at a concentration of 20 mg/ml)

TABLE 79 Perfusion containers of the second set having cyclophosphamide:Perfusion containers of second set Volume of solution in bag (ml) 75 100150 Cyclophosphamide amount per bag 750 1000 1500 (mg) (at aconcentration of 10 mg/ml)

TABLE 80 Perfusion containers of the third set having cyclophosphamide:Perfusion containers of third set Volume of solution in bag (ml) 50 75100 Cyclophosphamide amount per bag 250 375 500 (mg) (at a concentrationof 5 mg/ml)

In one particularly preferred embodiment wherein the antineoplastic drugis Cyclophosphamide, the first set of infusion containers compriseperfusion solution having Cyclophosphamide at a concentration rangingfrom about 5 mg/ml to 30 mg/ml and volume of solution ranging from about100 ml to about 1000 ml, further wherein the second or third set ofinfusion containers comprise perfusion solution having Cyclophosphamideat a concentration ranging from about 1-15 mg/ml and volume of solutionranging from about 30 ml to about 100 ml.

According to one embodiment, the dose of Cyclophosphamide for aparticular indication is 40 mg/kg based on body weight as the patientparameter. There is provided instructions for calculating the total doseto be delivered to a patient based on the body weight and instructionsfor selecting one or more perfusion containers of Cyclophosphamide fromdifferent sets, to deliver the calculated dose within ±5% variance andis presented in table (81):

TABLE 81 Description of perfusion system of Cyclophosphamide: First setof Perfusion Second set of Top-up perfusion container; cyclophosphamidecontainers; cyclophosphamide concentration 20 mg/ml concentration 10mg/ml: Total Target Volume of Dose delivered Volume Dose delivered %Variation** Body Dose to be perfusion from perfusion of top up fromtop-up Total dose from delivered Weight delivered container containercontainer container delivered dose Vs calculated (Kg) (mg) D (ml) (a)(mg) (ml) (b) (mg) (mg) (a + b) dose 50 2000.0 100 2000.00 0 0 2000.000.0 55 2200.0 105 2100.00 0 0 2100.00 −4.5 60 2400.0 115 2300.00 0 02300.00 −4.2 65 2600.0 125 2500.00 0 0 2500.00 −3.8 70 2800.0 1352700.00 0 0 2700.00 −3.6 75 3000.0 145 2900.00 0 0 2900.00 −3.3 803200.0 160 3200.00 0 0 3200.00 0.0 85 3400.0 115 2300.00 100 10003300.00 −2.9 90 3600.0 135 2700.00 100 1000 3700.00 2.8 95 3800.0 1352700.00 100 1000 3700.00 −2.6 100 4000.0 145 2900.00 100 1000 3900.00−2.5 **% Variation from delivered dose Vs calculated dose = [((a + b) −D]/D × 100

The containers of the perfusion system of Table (81) may be alphabeticalcoded as follows:

First set of Perfusion Second set of top-up perfusion containers;cyclophosphamide containers; cyclophosphamide concentration 0.85 mg/mlconcentration 0.5 mg/ml Volume of perfusion Alphabetical Volume of topup Alphabetical container (ml) code container (ml) code 100 A 100 H 105B 115 C 125 D 135 E 145 F 160 G

The perfusion system of Table (81) is accompanied by suitableinstructions for example as below:

Body Weight Instructions 50 Infuse the full volume from one 100 mlcontainer having an alphabetical code A 55 Infuse the full volume fromone 105 ml container having an alphabetical code B 60 Infuse the fullvolume from one 115 ml container having an alphabetical code C 65 Infusethe full volume from one 125 ml container having an alphabetical code D70 Infuse the full volume from one 135 ml container having analphabetical code E 75 Infuse the full volume from one 145 ml containerhaving an alphabetical code F 80 Infuse the full volume from one 160 mlcontainer having an alphabetical code G 85 Connect one 115 ml containerhaving an alphabetical code C with one 100 ml container having analphabetical code H and Infuse the full volume 90 and 95 Connect one 135ml container having an alphabetical code E with one 100 ml containerhaving an alphabetical code A and Infuse the full volume 100  Connectone 145 ml container having an alphabetical code F with one 100 mlcontainer having an alphabetical code H and Infuse the full volume

According to the instructions, one or more perfusion containers can beselected from first, second and/or third set of perfusion containers andfull volume is infused to deliver the calculated target dose within ±5%of variation.

1. A perfusion system for enabling hospitals or clinics to directlyadminister to patients in need thereof a dose of an antineoplastic drugcalculated according to a patient parameter, wherein the parametervaries over a range in the patient population, said system comprising:plurality of perfusion containers, each container comprising aready-to-infuse, aqueous perfusion solution of an antineoplastic drug,wherein said plurality of perfusion containers comprise a first set ofperfusion container (s) comprising a ready-to-infuse, aqueous perfusionsolution of an antineoplastic drug and a second set of top-up perfusioncontainers comprising a ready-to-infuse, aqueous perfusion solution ofthe antineoplastic drug and optionally a third set of top-up perfusioncontainers comprising a ready-to-infuse, aqueous perfusion solution ofthe antineoplastic drug, and instructions for selecting one or moreperfusion container(s) from the first set and if required one or moretop-up perfusion container(s) from the second and/or third set fordirectly administering the calculated dose of the antineoplastic drugfrom the selected perfusion containers.
 2. The perfusion system asclaimed in claim 1, wherein the first set of perfusion containerscomprises a ready-to-infuse, aqueous perfusion solution of anantineoplastic drug at a first concentration, the second set of top-upperfusion containers comprises a ready-to-infuse, aqueous perfusionsolution of the antineoplastic drug at a second concentration and theoptional third set of top-up perfusion containers comprises aready-to-infuse, aqueous perfusion solution of the antineoplastic drugat a third concentration.
 3. The perfusion system as claimed in claim 2,wherein the first, second and/or third concentrations are the same ordifferent.
 4. The perfusion system as claimed in claim 2, whereinvolumes of solution in the individual containers is the same ordifferent.
 5. The perfusion system as claimed in any of claims 1 to 4,wherein the patient parameter is selected from body surface area,body-weight, renal function or hepatic function.
 6. The perfusion systemas claimed in claim 2, wherein the first concentration, secondconcentration, and third concentration are different.
 7. The perfusionsystem as claimed in claim 6, wherein the first concentration is higherthan the second concentration and the second concentration is higherthan the third concentration.
 8. The perfusion system as claimed inclaim 2, wherein each of the first set of perfusion containers, thesecond set of top-up perfusion containers, and/or the third set oftop-up perfusion containers each comprise a plurality of containerscontaining different volumes of ready-to-infuse, aqueous perfusionsolution of an antineoplastic drug.
 9. The perfusion system as claimedin claim 8, wherein the first concentration is higher than the secondconcentration and the second concentration is higher than the thirdconcentration.
 10. A method for directly administering to a patient inneed thereof a dose of an antineoplastic drug calculated according to apatient parameter, wherein the parameter varies over a range in thepatient population, the method comprising the steps of: providing theperfusion system as claimed in claim 1; calculating the dose accordingto a patient parameter, selecting one or more perfusion container(s)from the first set of perfusion container(s) and if necessary from thesecond and/or third set of top-up perfusion container(s) required fordirectly administering the calculated dose and directly administering tothe patient in need thereof, the perfusion solution in the selectedcontainers.
 11. The method as claimed in claim 10, wherein the first setof perfusion containers comprises a ready-to-infuse, aqueous perfusionsolution of an antineoplastic drug at a first concentration, the secondset of top-up perfusion containers comprises a ready-to-infuse, aqueousperfusion solution of the antineoplastic drug at a second concentrationand the optional third set of top-up perfusion containers comprises aready-to-infuse, aqueous perfusion solution of the antineoplastic drugat a third concentration.
 12. The method as claimed in claim 11, whereinthe first, second and/or third concentrations are the same or different.13. The method as claimed in claim 11, wherein volumes of solution inthe individual containers is the same or different.
 14. The method asclaimed in any of claims 10 to 13, wherein the patient parameter isselected from body surface area, body-weight, renal function or hepaticfunction.
 15. The method as claimed in claim 11, wherein the firstconcentration, second concentration, and third concentration aredifferent.
 16. The method as claimed in claim 15, wherein the firstconcentration is higher than the second concentration and the secondconcentration is higher than the third concentration.
 17. The method asclaimed in claim 11, wherein each of the first set of perfusioncontainers, the second set of top-up perfusion containers, and/or thethird set of top-up perfusion containers each comprise a plurality ofcontainers containing different volumes of ready-to-infuse, aqueousperfusion solution of an antineoplastic drug.
 18. The method as claimedin claim 17, wherein the first concentration is higher than the secondconcentration and the second concentration is higher than the thirdconcentration.
 19. A perfusion container configured to be one ofperfusion containers in the perfusion system of claim 1, wherein theperfusion container comprises a ready to infuse perfusion solution of apartial dose of an antineoplastic drug for some patients in the patientpopulation, wherein the dose is calculated according to a patientparameter.
 20. A method for directly administering to a patient in needthereof a dose of an antineoplastic drug calculated according to apatient parameter, wherein the parameter varies over a range in thepatient population, the method comprising the steps of: providingperfusion container(s) as claimed in claim 19; calculating the doseaccording to a parameter for any given patient in the patientpopulation, selecting one or more perfusion containers from the firstset of perfusion container(s) and if necessary from the second or thirdset of perfusion containers, required for directly administering thecalculated dose, and directly administering to the patient in needthereof, the perfusion solution in the selected containers.
 21. Theperfusion system as claimed in claim 1 wherein the number of containersper set is 1 or 2
 22. The perfusion system as claimed in claim 21wherein the number of containers per set is
 1. 23. The method accordingto claim 10 wherein the number of containers per set is 1 or 2
 24. Themethod according to claim 23 wherein the number of containers per setis
 1. 25. A perfusion container for directly administering to patients adose of an antineoplastic drug calculated according to a patient'sparameter, wherein the first perfusion container comprises a solution ofantineoplastic drug at a concentration and volume such that the amountof antineoplastic drug in the container is equal to the calculated dosefor one patient but less than the calculated dose for a second patient,the calculated dose is provided to first patient within 5% variance bydirectly administering the full volume of the solution of antineoplasticdrug from the first perfusion container, further the first perfusioncontainer is accompanied by a second top-up perfusion containercomprising a solution of antineoplastic drug at a concentration andvolume such that the calculated dose is provided within 5% variance bydirectly administering the full volume of the solution of antineoplasticdrug from the first perfusion container and the second top-up containerto the second patient.
 26. A perfusion container as claimed in claim 25wherein the concentration in the first perfusion container and theconcentration in the second top-up perfusion container is same.
 27. Aperfusion container as claimed in claim 25 wherein the concentration inthe first perfusion container is higher than the concentration in thesecond top-up perfusion container.
 28. A perfusion container as claimedin claim 25 wherein the volume in the first perfusion container and thevolume in the second top-up perfusion container is same.
 29. A perfusioncontainer as claimed in claim 25 wherein the volume in the perfusioncontainer is higher than the volume in the second top-up perfusioncontainer.